We investigated hemostatic function in patients with cerebral ischemia by evaluating platelet activation, fibrin generation, and fibrinolysis. Plasma beta-thromboglobulin, an index of platelet activation, was significantly increased both acutely (14.9 +/- 9.2 ng/mL; n = 85) and approximately 2 months later (17.3 +/- 10.1 ng/mL; n = 57). Thrombin activity was measured using assays for fibrinopeptide A and fibrin D-dimer. Increased fibrinopeptide A was found in 9 (11.5%) of 78 patients acutely and 6 (10.7%) of 56 at follow-up; fibrin D-dimer levels were significantly increased acutely (166 +/- 188 ng/mL; n = 66) but not at follow-up. Fibrinolytic activity was measured using assays for fibrinopeptide B-beta 1-42 and plasminogen activator inhibitor 1. Fibrinopeptide B-beta 1-42 was significantly reduced acutely (6.3 +/- 2.2 pmol/mL; n = 35) and at follow-up (4.8 +/- 1.5 pmol/mL; n = 21). Plasminogen activator inhibitor 1 was normal acutely (20.1 +/- 12.0 ng/mL; n = 73) but increased at follow-up (27.8 +/- 20.1 ng/mL; n = 45). These results demonstrate that patients with cerebral ischemia have abnormal hemostatic function that is not explained by the acute phase reaction, and that components of the prethrombotic state are present in some of these patients.