Platelet primary hemostatic function occurs under high shear conditions. Cyclooxygenase inhibitors such as ibuprofen inhibit this platelet aggregation under high shear rates only to a limited extent. This prompted the present study on 10 healthy volunteers treated with 100 mg aspirin for 4 weeks. The platelet function analyser (PFA-100) was used to measure the closure time (CT) of a membrane pore coated with collagen and epinephrine by aggregating platelets under shear rates of 5000-6000 s(-1). A first dose of 100 mg aspirin prolonged the CT above the normal range in 4 of 10 individuals, but the CT for the whole group (153+/-42 s) was not different from baseline (112+/-18 s). After 7 and 28 days of treatment, CTs were >300 s in 8 individuals and the mean values for the group were significantly higher than baseline. However, one subject had an intermediate response and one had an aspirin non-responsiveness, which was not overcome by 300 mg aspirin daily. The CT was normalized in 4 individuals 48 h after the last aspirin dose and in 7 individuals after 72 h, when the mean value for the group became not different from baseline. We conclude that the platelet function measured with the PFA-100 is not inhibited significantly after a single dose of 100 mg aspirin, is thereafter inhibited consistently in the majority, but not all individuals during a 4 week treatment, and returns to normal in 48-72 h. Since large interindividual differences exist, monitoring of platelet inhibition at the beginning of an aspirin treatment should be considered and validated in a prospective study.