Background: Platelet-derived microparticles (PMPs) are generally considered a marker of platelet activation in cardiovascular disease. We studied the extent to which PMP subpopulations parallel platelet activation in vitro and in vivo. Methods: Using flow cytometry, we analyzed PMP subpopulations from resting and activated platelets in vitro (n ؍ 6) as well as from plasma samples of patients with stable angina, peripheral arterial disease, or myocardial infarction [non-ST-elevation (NSTEMI) and ST-elevation (STEMI)] and from older, age-and sexmatched and young healthy individuals [n ؍ 10 for all groups except NSTEMI (n ؍ 11)]. Coagulation markers prothrombin fragment F 1 ؉ 2 and thrombin-antithrombin complexes were determined by ELISA. The PMPassociated fraction of soluble (s)P-selectin was estimated by ELISA. Results: In vitro, stimulation of platelets with thrombin receptor-activating peptide (15 mol/L) or the calcium ionophore A23187 (2.5 mol/L) increased fractions of both platelets and PMPs exposing P-selectin or CD63 (P <0.001 for all). Whereas the number of PMPs released by A23187-stimulated platelets increased significantly (P <0.001), the number of PMPs released from thrombin receptor-activating peptide-stimulated platelets remained constant (P >0.05). Ex vivo, numbers of circu-