USMLE Step 1 Practice Questions
This is a free 15-question basic science sampler written by the StudyPDF team in the spirit of USMLE Step 1. It moves across biochemistry and genetics, microbiology and immunology, pharmacology principles, pathology and pathophysiology, physiology, neuroanatomy, behavioral science and biostatistics, mixing multiple choice, select all that apply and fill in the blank. Every question asks about a mechanism or a piece of reasoning rather than a treatment decision. Answer all 15, then check your score and read the explanation for each one.
A newborn screening test flags high blood phenylalanine. Which enzyme is deficient in classic phenylketonuria?
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All 15 questions at a glance
Prefer to read before you play? Every question in the sampler is listed below. Answers and explanations stay collapsed until you open them.
1. A newborn screening test flags high blood phenylalanine. Which enzyme is deficient in classic phenylketonuria?
- A. Phenylalanine hydroxylase
- B. Tyrosinase
- C. Homogentisate oxidase
- D. Branched chain alpha ketoacid dehydrogenase
Show answer and explanation
Answer: A. Phenylalanine hydroxylase
Phenylalanine hydroxylase converts phenylalanine to tyrosine using tetrahydrobiopterin as a cofactor. When it is missing, phenylalanine builds up and tyrosine becomes an essential amino acid that has to come from the diet. The other enzymes map to different diseases: tyrosinase to albinism, homogentisate oxidase to alkaptonuria, and branched chain alpha ketoacid dehydrogenase to maple syrup urine disease.
2. In a family pedigree, every child of an affected woman has the condition, while no child of an affected man has it. Which inheritance pattern does this fit?
- A. Autosomal dominant
- B. X linked recessive
- C. Mitochondrial
- D. Autosomal recessive
Show answer and explanation
Answer: C. Mitochondrial
Mitochondria are inherited from the egg, so a mother passes her mitochondrial DNA to all of her children and a father passes none of his. Severity often varies within the same family because of heteroplasmy, meaning the proportion of mutated mitochondria differs from cell to cell. Autosomal dominant transmission would come from either parent to about half the children, which is not what this pedigree shows.
3. Complete the sentence.
A test with high _____ is most useful for ruling a disease out when the result is negative, while a test with high _____ is most useful for ruling it in when the result is positive.
Options for blank 1: sensitivity, specificity, precision
Options for blank 2: reliability, specificity, precision, sensitivity
Show answer and explanation
Answer: sensitivity, specificity
Sensitivity is the fraction of people with the disease that the test calls positive, so a very sensitive test misses almost nobody and a negative result carries weight. Specificity is the fraction of healthy people the test calls negative, so a very specific test rarely cries wolf and a positive result carries weight. The usual shorthand is that a sensitive test rules out and a specific test rules in.
4. The same diagnostic test is moved from a specialty clinic where the disease is common to a general screening population where it is rare. What happens?
- A. Sensitivity falls and specificity rises
- B. Positive predictive value falls while sensitivity and specificity stay the same
- C. Positive predictive value stays the same because it is a fixed property of the test
- D. Negative predictive value falls
Show answer and explanation
Answer: B. Positive predictive value falls while sensitivity and specificity stay the same
Sensitivity and specificity are properties of the test itself and do not move with prevalence. Predictive values do. When prevalence drops, more of the positives are false positives, so positive predictive value falls while negative predictive value rises. This is why screening a low risk population with an imperfect test produces so many positives that turn out to be nothing.
5. Which of the following statements describe a case control study?
Select all that apply.
- A. It starts with people who already have the outcome and looks backward at exposure
- B. It measures the incidence of new disease directly
- C. It reports an odds ratio rather than a relative risk
- D. It is an efficient design for studying a rare disease
- E. It follows disease free people forward in time until the outcome appears
Show answer and explanation
Answer: A. It starts with people who already have the outcome and looks backward at exposure, C. It reports an odds ratio rather than a relative risk, D. It is an efficient design for studying a rare disease
A case control study picks cases and matched controls first, then asks about past exposure, which makes it fast and cheap for rare outcomes. Because the investigator chose how many cases to enroll, the design cannot measure incidence, so the effect measure is an odds ratio. Following disease free people forward and measuring incidence describes a cohort study, and recall bias is the classic threat to the case control design.
6. Diphtheria toxin and Pseudomonas aeruginosa exotoxin A kill host cells by the same mechanism. Which one?
- A. They cleave SNARE proteins and block neurotransmitter release
- B. They bind MHC class II and the T cell receptor outside the antigen binding groove
- C. They raise cyclic AMP by ADP ribosylating the Gs alpha subunit
- D. They ADP ribosylate elongation factor 2 and shut down protein synthesis
Show answer and explanation
Answer: D. They ADP ribosylate elongation factor 2 and shut down protein synthesis
Both toxins transfer an ADP ribose group onto elongation factor 2, which halts translation and kills the cell. The other options are real mechanisms belonging to other toxins: SNARE cleavage is tetanus and botulinum toxin, superantigen binding is toxic shock syndrome toxin and streptococcal pyrogenic exotoxin A, and ADP ribosylation of Gs alpha is cholera toxin.
7. A young boy has recurrent abscesses with catalase positive organisms, and a dihydrorhodamine flow cytometry test is abnormal. What is the underlying defect?
- A. Defective NADPH oxidase in phagocytes
- B. Failed B cell maturation from a BTK mutation
- C. CD18 deficiency preventing leukocyte adhesion
- D. Deficiency of the terminal complement components C5 through C9
Show answer and explanation
Answer: A. Defective NADPH oxidase in phagocytes
Chronic granulomatous disease comes from a defective NADPH oxidase, so phagocytes cannot generate the respiratory burst that normally produces superoxide. Catalase positive organisms are the problem because they destroy their own hydrogen peroxide, leaving the phagocyte with nothing to borrow. The dihydrorhodamine test measures that burst directly, which is why it is abnormal here.
8. Which mechanism defines a type II hypersensitivity reaction?
- A. IgE bound to mast cells cross linked by antigen
- B. IgG or IgM directed against an antigen on a cell surface or in the matrix
- C. Antigen antibody complexes depositing in tissue and activating complement
- D. Sensitized T cells releasing cytokines that recruit macrophages
Show answer and explanation
Answer: B. IgG or IgM directed against an antigen on a cell surface or in the matrix
Type II is antibody against a fixed target, so the damage is local to the cell or tissue carrying that antigen, through complement lysis, opsonization or interference with receptor function. Type I is the IgE and mast cell route, type III is circulating immune complexes that deposit wherever the blood takes them, and type IV is cell mediated and takes a day or more to appear.
9. A drug binds the same site as an agonist but produces no response of its own. What does it do to the agonist dose response curve?
- A. It lowers the maximal response and cannot be overcome by more agonist
- B. It shifts the curve to the left and raises agonist potency
- C. It binds a separate site and lowers the maximal response
- D. It shifts the curve to the right with the maximal response unchanged
Show answer and explanation
Answer: D. It shifts the curve to the right with the maximal response unchanged
That description is a competitive antagonist. It competes for the same binding site, so enough agonist can outcompete it and still reach the full maximal effect, which shows up as a rightward shift with an unchanged plateau. A noncompetitive or irreversible antagonist behaves the way the other options describe, lowering the maximal response no matter how much agonist you add.
10. Which drug and characteristic toxicity pairings are correct?
Select all that apply.
- A. Aminoglycosides and ototoxicity
- B. Vincristine and hemorrhagic cystitis
- C. Bleomycin and pulmonary fibrosis
- D. Cisplatin and vitamin B12 deficiency
- E. Doxorubicin and dilated cardiomyopathy
Show answer and explanation
Answer: A. Aminoglycosides and ototoxicity, C. Bleomycin and pulmonary fibrosis, E. Doxorubicin and dilated cardiomyopathy
Aminoglycosides damage the hair cells of the inner ear and the kidney, bleomycin causes lung injury that can progress to fibrosis, and the anthracyclines cause a dose related dilated cardiomyopathy driven by free radical damage to myocardium. The two wrong pairs belong elsewhere: hemorrhagic cystitis is the classic cyclophosphamide toxicity from acrolein, and vincristine causes peripheral neuropathy. Cisplatin is nephrotoxic and ototoxic, not a cause of B12 deficiency.
11. Complete the sentence.
Nitric oxide relaxes vascular smooth muscle by activating guanylate cyclase, which raises intracellular _____.
Options for blank 1: cyclic AMP, cyclic GMP, inositol trisphosphate, calcium
Show answer and explanation
Answer: cyclic GMP
Nitric oxide diffuses from the endothelium into the smooth muscle cell and switches on soluble guanylate cyclase, so cyclic GMP rises and the cell relaxes. Phosphodiesterase type 5 breaks that cyclic GMP down, which is why inhibiting the enzyme amplifies the same pathway. Cyclic AMP and inositol trisphosphate are second messengers for different receptor families.
12. A urinalysis shows red blood cell casts and dysmorphic red cells with mild proteinuria, and the blood pressure is high. Which process does this pattern point to?
- A. Nephrotic syndrome from podocyte injury
- B. A lower urinary tract infection
- C. Glomerular inflammation, the nephritic pattern
- D. Prerenal azotemia from volume loss
Show answer and explanation
Answer: C. Glomerular inflammation, the nephritic pattern
Red cell casts form inside the tubule, so they prove the bleeding came from the glomerulus rather than lower down, and that inflammatory picture with hypertension is the nephritic pattern. The nephrotic pattern is the opposite balance, with heavy proteinuria above roughly 3.5 grams per day, low albumin, edema and fatty casts, and a bland sediment. Learning the two sediments as a pair is faster than memorizing each disease separately.
13. Which findings fit an obstructive pattern on pulmonary function testing?
Select all that apply.
- A. A reduced FEV1 to FVC ratio
- B. An increased total lung capacity from air trapping
- C. An increased FEV1 to FVC ratio
- D. A prolonged expiratory phase
- E. A reduced total lung capacity with a normal FEV1 to FVC ratio
Show answer and explanation
Answer: A. A reduced FEV1 to FVC ratio, B. An increased total lung capacity from air trapping, D. A prolonged expiratory phase
Obstruction means air leaves slowly, so FEV1 falls more than FVC, the ratio drops, expiration takes longer and air stays trapped, which raises residual volume and total lung capacity. Restriction is the mirror image: the lungs are small, so both FEV1 and FVC fall together and the ratio is normal or even high. Reading the ratio first and the volumes second sorts almost every pulmonary function question quickly.
14. Which pathway carries pain and temperature sensation, and where does it cross the midline?
- A. The dorsal column and medial lemniscus pathway, crossing in the medulla
- B. The lateral corticospinal tract, crossing in the medulla
- C. The spinothalamic tract, crossing in the spinal cord within a segment or two of where the fiber enters
- D. The dorsal spinocerebellar tract, which does not cross at all
Show answer and explanation
Answer: C. The spinothalamic tract, crossing in the spinal cord within a segment or two of where the fiber enters
Pain and temperature fibers synapse in the dorsal horn and then cross almost immediately in the anterior white commissure before ascending in the spinothalamic tract. Fine touch, vibration and proprioception travel up the same side in the dorsal columns and only cross in the medulla. That difference in crossing level is what produces the split findings of a spinal cord hemisection, with loss of pain and temperature on the opposite side and loss of vibration and position sense on the same side.
15. Complete the sentence.
Attributing your own unacceptable impulse or feeling to somebody else is the immature defense mechanism called _____.
Options for blank 1: displacement, sublimation, projection, reaction formation
Show answer and explanation
Answer: projection
Projection puts the disowned feeling onto another person, as when someone who resents a colleague insists the colleague resents them. Displacement moves the feeling onto a safer target instead, reaction formation replaces it with the opposite behavior, and sublimation channels it into something socially useful, which makes sublimation the one mature mechanism in this list.
What USMLE Step 1 actually tests
Step 1 is the first of the three United States Medical Licensing Examination steps, and it is sponsored jointly by the National Board of Medical Examiners and the Federation of State Medical Boards. StudyPDF is not affiliated with either organization. The exam is delivered at Prometric test centers in a single eight hour session, with a maximum of 280 items split across timed blocks. The block layout changed in 2026, so check the exam structure page on usmle.org for the version that applies to your own test date.
Since January 2022 Step 1 has been reported as pass or fail, with no three digit score. That change did not make the exam easier, but it did change the strategy around it. Chasing a higher number no longer buys anything, so the sane target is solid, broad competence across the whole outline instead of squeezing the last few points out of one favorite subject.
The content is organized along two dimensions, systems and processes, and it is deliberately integrated. A single item can pull a genetics concept, a drug mechanism and an organ system finding into one vignette. The published content outline on usmle.org lists the disciplines and their approximate weighting.
How to use this sampler and how to study basic science
These 15 questions are compact rather than full length vignettes, and they stay on the basic science side on purpose. They ask which enzyme is missing, which receptor a drug acts on, what a lab pattern implies, and what happens to predictive value when prevalence drops. Clinical knowledge and management reasoning belong to Step 2, and the sibling quiz linked below covers that ground. This page is exam practice written by the StudyPDF team. It is not medical guidance, it is not a source for patient care decisions, and none of these are real exam items.
Take the sampler in one sitting without notes, then read every explanation, including the ones you answered correctly. A miss is a topic, not a fact. If you drop the sensitivity question and the predictive value question, the fix is one afternoon on test characteristics, not two flashcards.
For the exam itself, the study pattern that works is a long timeline of mixed practice questions with spaced review, not a single pass through a review book. Do questions in random order across subjects so you have to recognize what the stem is really testing, and keep a running list of the concepts you miss.
How StudyPDF builds practice questions from your own materials
Fifteen questions can show you where the gaps are. They cannot get you ready for an eight hour exam, and no fixed bank matches the emphasis of your own school, your own lecture notes or the review book sitting on your desk.
StudyPDF works from your material instead. You upload your lecture slides, your pathology handouts, a course packet or the review book you already own, and Bo, the study agent, writes practice questions from those exact pages. Every question is grounded in what you uploaded, and every explanation points back to where the answer came from, so you can go straight to the source when something looks wrong. You can regenerate as often as you like, narrow a set to one system such as renal or endocrine, and track which concepts keep tripping you up.
You do not need a document to start. If you have nothing to upload, just name a topic instead, for example glycogen storage diseases, beta lactam mechanisms or the hypersensitivity types, and Bo writes a set from that. Starting is free.
Written by the StudyPDF team. Last updated 2026-08-19.