This randomized, double-blind, parallel-group study was performed to assess the effect of 1-week treatment with 75 and 300 mg aspirin on thrombin generation. Eighteen healthy men, aged 20-25 years, entered the study. After 1 week of aspirin treatment with a daily dose of 75 mg, bleeding time became prolonged by 102 s (P = 0.02), and it was prolonged by 165 s with 300 mg (P = 0.0005). None of the doses of aspirin affected peripheral blood concentrations of prothrombin fragment 1+2 and fibrinopeptide A. At the site of microvascular injury, 75 mg aspirin led to a marked, about 60%, reduction in the total amount of thrombin generated (P = 0.04). A similar decrease was observed after 7-day treatment with 300 mg aspirin (P = 0.009). We conclude that the thrombin-lowering action of aspirin in the range between 75 and 300 mg daily given for 7 days is not dose dependent.