1
USMLE Step 1 Practice Exam 2025
– 200 High-Level Questions with
100% Verified Answers & Expert
Rationales | A+ Graded
Student Name: _________________________
Date: _______________
Time Limit: 240 minutes
Total Questions: 200
Question 1 (Single-Select)
A 25-year-old male presents with a fracture of the proximal humerus. Which nerve is most likely
at risk of injury?
A. Radial nerve
B. Axillary nerve
C. Ulnar nerve
D. Median nerve
Correct Answer: B. Axillary nerve
Rationale: The axillary nerve (C5-C6) innervates the deltoid and teres minor and provides
sensation to the lateral shoulder. It is at risk in proximal humerus fractures or shoulder
dislocations due to its proximity to the surgical neck of the humerus. The radial nerve (A) is
more vulnerable in midshaft humerus fractures, while the ulnar (C) and median (D) nerves are
not typically affected in this region.
Question 2 (Single-Select)
A 30-year-old female with a history of recurrent urinary tract infections is prescribed
nitrofurantoin. What is the primary mechanism of action of this drug?
A. Inhibits bacterial cell wall synthesis
B. Damages bacterial DNA via reactive intermediates
, 2
C. Inhibits bacterial protein synthesis
D. Disrupts bacterial folate synthesis
Correct Answer: B. Damages bacterial DNA via reactive intermediates
Rationale: Nitrofurantoin is reduced by bacterial enzymes into reactive intermediates that
damage bacterial DNA, leading to cell death. It is effective against urinary tract pathogens. Cell
wall synthesis (A) is targeted by penicillins, protein synthesis (C) by aminoglycosides, and folate
synthesis (D) by trimethoprim-sulfamethoxazole.
Question 3 (Single-Select)
A 45-year-old male presents with chest pain and is diagnosed with myocardial infarction. Which
enzyme is most specific for confirming this diagnosis?
A. Creatine kinase-MB (CK-MB)
B. Aspartate aminotransferase (AST)
C. Lactate dehydrogenase (LDH)
D. Cardiac troponin I
Correct Answer: D. Cardiac troponin I
Rationale: Cardiac troponin I is the most specific and sensitive biomarker for myocardial
infarction, remaining elevated for 7-10 days. CK-MB (A) is less specific and normalizes within
2-3 days. AST (B) and LDH (C) are non-specific and elevated in multiple conditions, including
liver and muscle injury.
Question 4 (Single-Select)
A 22-year-old male with sickle cell anemia experiences a vaso-occlusive crisis. Which of the
following is the primary cause of his symptoms?
A. Increased red blood cell membrane fluidity
B. Polymerization of deoxygenated hemoglobin S
C. Decreased bone marrow erythropoiesis
D. Autoimmune hemolysis
Correct Answer: B. Polymerization of deoxygenated hemoglobin S
Rationale: Sickle cell anemia results from a point mutation in the beta-globin gene, causing
hemoglobin S to polymerize under low oxygen conditions. This leads to rigid, sickle-shaped
RBCs that obstruct blood flow, causing vaso-occlusive crises. Membrane fluidity (A) is not
affected, erythropoiesis (C) is increased, and hemolysis (D) is not autoimmune.
, 3
Question 5 (Single-Select)
A 35-year-old female presents with fatigue and is found to have a serum TSH of 10 mU/L and
low free T4. What is the most likely diagnosis?
A. Graves’ disease
B. Primary hypothyroidism
C. Secondary hyperthyroidism
D. Subclinical hyperthyroidism
Correct Answer: B. Primary hypothyroidism
Rationale: Elevated TSH with low free T4 indicates primary hypothyroidism, often due to
Hashimoto’s thyroiditis or iodine deficiency. Graves’ disease (A) causes hyperthyroidism (low
TSH, high T4). Secondary hyperthyroidism (C) involves high TSH and high T4 due to a pituitary
tumor. Subclinical hyperthyroidism (D) shows low TSH with normal T4.
Question 6 (Single-Select)
A 28-year-old male is diagnosed with tuberculosis. Which drug inhibits mycobacterial cell wall
synthesis by blocking mycolic acid formation?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol
Correct Answer: A. Isoniazid
Rationale: Isoniazid inhibits mycolic acid synthesis, a critical component of the mycobacterial
cell wall, by targeting the enzyme InhA. Rifampin (B) inhibits RNA polymerase, pyrazinamide
(C) disrupts membrane energetics, and ethambutol (D) inhibits arabinosyl transferase, affecting
cell wall polysaccharide synthesis.
Question 7 (Single-Select)
A 40-year-old male with chronic alcoholism presents with confusion and ataxia. Which vitamin
deficiency is most likely responsible?
A. Vitamin B1 (thiamine)
B. Vitamin B6 (pyridoxine)
, 4
C. Vitamin B12 (cobalamin)
D. Vitamin C
Correct Answer: A. Vitamin B1 (thiamine)
Rationale: Thiamine deficiency in alcoholics leads to Wernicke’s encephalopathy, characterized
by confusion, ataxia, and ophthalmoplegia. Vitamin B6 deficiency (B) causes peripheral
neuropathy, B12 deficiency (C) causes subacute combined degeneration, and vitamin C
deficiency (D) causes scurvy.
Question 8 (Single-Select)
A 50-year-old female presents with a mass in the right breast. Biopsy reveals invasive ductal
carcinoma. Which receptor status is associated with the best prognosis?
A. ER-positive, PR-positive, HER2-negative
B. ER-negative, PR-negative, HER2-positive
C. ER-negative, PR-negative, HER2-negative
D. ER-positive, PR-negative, HER2-positive
Correct Answer: A. ER-positive, PR-positive, HER2-negative
Rationale: Estrogen receptor (ER) and progesterone receptor (PR) positivity with HER2
negativity indicates a luminal A subtype, which has the best prognosis due to responsiveness to
hormonal therapies like tamoxifen. Triple-negative (C) and HER2-positive (B, D) tumors are
more aggressive and have worse outcomes.
Question 9 (Single-Select)
A 19-year-old male presents with fever, sore throat, and lymphadenopathy. Monospot test is
positive. Which virus is most likely responsible?
A. Cytomegalovirus
B. Epstein-Barr virus
C. Human immunodeficiency virus
D. Herpes simplex virus
Correct Answer: B. Epstein-Barr virus
Rationale: A positive Monospot test indicates infectious mononucleosis, caused by Epstein-Barr
virus (EBV). CMV (A) can cause a similar syndrome but is Monospot-negative. HIV (C)
presents with acute retroviral syndrome, and HSV (D) causes mucocutaneous lesions.
USMLE Step 1 Practice Exam 2025
– 200 High-Level Questions with
100% Verified Answers & Expert
Rationales | A+ Graded
Student Name: _________________________
Date: _______________
Time Limit: 240 minutes
Total Questions: 200
Question 1 (Single-Select)
A 25-year-old male presents with a fracture of the proximal humerus. Which nerve is most likely
at risk of injury?
A. Radial nerve
B. Axillary nerve
C. Ulnar nerve
D. Median nerve
Correct Answer: B. Axillary nerve
Rationale: The axillary nerve (C5-C6) innervates the deltoid and teres minor and provides
sensation to the lateral shoulder. It is at risk in proximal humerus fractures or shoulder
dislocations due to its proximity to the surgical neck of the humerus. The radial nerve (A) is
more vulnerable in midshaft humerus fractures, while the ulnar (C) and median (D) nerves are
not typically affected in this region.
Question 2 (Single-Select)
A 30-year-old female with a history of recurrent urinary tract infections is prescribed
nitrofurantoin. What is the primary mechanism of action of this drug?
A. Inhibits bacterial cell wall synthesis
B. Damages bacterial DNA via reactive intermediates
, 2
C. Inhibits bacterial protein synthesis
D. Disrupts bacterial folate synthesis
Correct Answer: B. Damages bacterial DNA via reactive intermediates
Rationale: Nitrofurantoin is reduced by bacterial enzymes into reactive intermediates that
damage bacterial DNA, leading to cell death. It is effective against urinary tract pathogens. Cell
wall synthesis (A) is targeted by penicillins, protein synthesis (C) by aminoglycosides, and folate
synthesis (D) by trimethoprim-sulfamethoxazole.
Question 3 (Single-Select)
A 45-year-old male presents with chest pain and is diagnosed with myocardial infarction. Which
enzyme is most specific for confirming this diagnosis?
A. Creatine kinase-MB (CK-MB)
B. Aspartate aminotransferase (AST)
C. Lactate dehydrogenase (LDH)
D. Cardiac troponin I
Correct Answer: D. Cardiac troponin I
Rationale: Cardiac troponin I is the most specific and sensitive biomarker for myocardial
infarction, remaining elevated for 7-10 days. CK-MB (A) is less specific and normalizes within
2-3 days. AST (B) and LDH (C) are non-specific and elevated in multiple conditions, including
liver and muscle injury.
Question 4 (Single-Select)
A 22-year-old male with sickle cell anemia experiences a vaso-occlusive crisis. Which of the
following is the primary cause of his symptoms?
A. Increased red blood cell membrane fluidity
B. Polymerization of deoxygenated hemoglobin S
C. Decreased bone marrow erythropoiesis
D. Autoimmune hemolysis
Correct Answer: B. Polymerization of deoxygenated hemoglobin S
Rationale: Sickle cell anemia results from a point mutation in the beta-globin gene, causing
hemoglobin S to polymerize under low oxygen conditions. This leads to rigid, sickle-shaped
RBCs that obstruct blood flow, causing vaso-occlusive crises. Membrane fluidity (A) is not
affected, erythropoiesis (C) is increased, and hemolysis (D) is not autoimmune.
, 3
Question 5 (Single-Select)
A 35-year-old female presents with fatigue and is found to have a serum TSH of 10 mU/L and
low free T4. What is the most likely diagnosis?
A. Graves’ disease
B. Primary hypothyroidism
C. Secondary hyperthyroidism
D. Subclinical hyperthyroidism
Correct Answer: B. Primary hypothyroidism
Rationale: Elevated TSH with low free T4 indicates primary hypothyroidism, often due to
Hashimoto’s thyroiditis or iodine deficiency. Graves’ disease (A) causes hyperthyroidism (low
TSH, high T4). Secondary hyperthyroidism (C) involves high TSH and high T4 due to a pituitary
tumor. Subclinical hyperthyroidism (D) shows low TSH with normal T4.
Question 6 (Single-Select)
A 28-year-old male is diagnosed with tuberculosis. Which drug inhibits mycobacterial cell wall
synthesis by blocking mycolic acid formation?
A. Isoniazid
B. Rifampin
C. Pyrazinamide
D. Ethambutol
Correct Answer: A. Isoniazid
Rationale: Isoniazid inhibits mycolic acid synthesis, a critical component of the mycobacterial
cell wall, by targeting the enzyme InhA. Rifampin (B) inhibits RNA polymerase, pyrazinamide
(C) disrupts membrane energetics, and ethambutol (D) inhibits arabinosyl transferase, affecting
cell wall polysaccharide synthesis.
Question 7 (Single-Select)
A 40-year-old male with chronic alcoholism presents with confusion and ataxia. Which vitamin
deficiency is most likely responsible?
A. Vitamin B1 (thiamine)
B. Vitamin B6 (pyridoxine)
, 4
C. Vitamin B12 (cobalamin)
D. Vitamin C
Correct Answer: A. Vitamin B1 (thiamine)
Rationale: Thiamine deficiency in alcoholics leads to Wernicke’s encephalopathy, characterized
by confusion, ataxia, and ophthalmoplegia. Vitamin B6 deficiency (B) causes peripheral
neuropathy, B12 deficiency (C) causes subacute combined degeneration, and vitamin C
deficiency (D) causes scurvy.
Question 8 (Single-Select)
A 50-year-old female presents with a mass in the right breast. Biopsy reveals invasive ductal
carcinoma. Which receptor status is associated with the best prognosis?
A. ER-positive, PR-positive, HER2-negative
B. ER-negative, PR-negative, HER2-positive
C. ER-negative, PR-negative, HER2-negative
D. ER-positive, PR-negative, HER2-positive
Correct Answer: A. ER-positive, PR-positive, HER2-negative
Rationale: Estrogen receptor (ER) and progesterone receptor (PR) positivity with HER2
negativity indicates a luminal A subtype, which has the best prognosis due to responsiveness to
hormonal therapies like tamoxifen. Triple-negative (C) and HER2-positive (B, D) tumors are
more aggressive and have worse outcomes.
Question 9 (Single-Select)
A 19-year-old male presents with fever, sore throat, and lymphadenopathy. Monospot test is
positive. Which virus is most likely responsible?
A. Cytomegalovirus
B. Epstein-Barr virus
C. Human immunodeficiency virus
D. Herpes simplex virus
Correct Answer: B. Epstein-Barr virus
Rationale: A positive Monospot test indicates infectious mononucleosis, caused by Epstein-Barr
virus (EBV). CMV (A) can cause a similar syndrome but is Monospot-negative. HIV (C)
presents with acute retroviral syndrome, and HSV (D) causes mucocutaneous lesions.
