To evaluate the effects of aspirin on thrombin generation in patients with unstable angina, plasma levels of thrombin-antithrombin III complex (TAT) as a new marker of thrombin generation and of 11-dehydro-thromboxane B 2 (11-dehydro-TXB 2) as an indicator of platelet activation were measured in 18 patients with unstable angina, including 8 patients with prolonged rest angina (> 15 minutes). Aspirin DL-lysine (900 mg) was administered intravenously to 9 of the 18 patients (aspirin group); the other 9 were not given aspirin during the first 24 hours of hospitalization (non-aspirin group). Clinical characteristics, angiographic features and medications other than aspirin were similar between the 2 groups. Levels of plasma TAT and 11-dehydro-TXB 2 were significantly higher (p < 0.05) in patients with prolonged rest angina than in those without the condition (n = 10). In 5 patients with prolonged rest angina who received aspirin, plasma TAT levels (ng/ml) were significantly decreased (4.52 ± 1.18 at baseline, 2.50 ± 0.65 at 1 hour and 2.16 ± 0.42 at 24 hours after aspirin administration, p < 0.01) with a significant decrease in plasma 11-dehydro-TXB 2 levels. However, the reduction in TAT after aspirin administration was slight in patients without prolonged rest angina (n = 4). In contrast, levels of plasma TAT and 11-dehydro-TXB 2 in the non-aspirin group remained unchanged during the study period. These results suggest that aspirin rapidly reduces thrombin generation through inhibition of platelet activity in patients with unstable angina with prolonged rest angina.