Thrombin and platelets are directly involved in arterial thrombosis, typically occurring at sites of atherosclerotic plaque rupture among patients with acute coronary syndromes. Understanding the dynamic nature of pathologic thrombosis has important clinical implications. Methods: Fibrinopeptide A (FPA), thrombin-antithrombin complexes (TAT), and prothrombin activation fragment 1.2 (F1.2), plasma markers of fibrin formation (thrombin activity) and thrombin generation, and platelet activation, determined by the recognition of a surface-expressed platelet alpha-granule protein, P-selectin, using flow cytometry, were measured in 36 consecutive patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis In Myocardial Ischemia (TIMI) III B trial. Results: Thrombin generation (TAT 12.1 +/- 17.8 ng/ml vs. 3.4 +/- 1.0 ng/ml; F1.2 0.19 +/- 0.14 nmol/l vs. 0.12 +/- 0.8 nmol/l), fibrin formation (FPA 15.8 +/- 23.5 ng/ml vs. 7.5 +/- 2.3 ng/ml), and platelet activation) 10.6 +/- 2.4% vs. 2.5 +/- 2.0%) were increased significantly in patients compared with healthy, age-matched controls (p < 0.01). Fibrin formation, represented by plasma FPA levels, did not correlate with the percentage of activated platelets (r = -.10, p = 0.69). Thrombin generation and platelet activation also did not correlate. A statistically insignificant trend between TAT and platelet activation was observed (r =.42, p = 0.07); however, even with TAT levels in excess of 20 ng/ml (nearly sixfold greater than normal healthy controls) platelet activation was increased by only 1.7-fold. Conclusions: Thrombin generation, fibrin formation, and platelet activation are increased modestly among patients with unstable angina and non-Q-wave myocardial infarction. Despite the involvement of platelets and coagulation proteins in arterial thrombotic processes, their relative contributions may vary, providing a pathophysiologic basis for the dynamic expression of di sease and response to treatment observed commonly in clinical practice.