This study was designed to determine in patients with unstable angina whether specific electrocardiographic abnormalities associated with ischemia, the presence of coronary lesions consistent with thrombosis on angiography or the presence of recurrent ischemia reflects increases in thrombin activity as manifested by increased plasma concentrations of fibrinopeptide A. The concentration of fibrinopeptide A in plasma was increased to 6.7 ± 3.1 nM for the group as a whole (n = 29). Increases were greater in the 17 patients who exhibited reversible ST segment shifts (10.2 ± 5.2 nM) than in the 12 patients exhibiting reversible T wave abnormalities alone (1.6 ± 0.2 nM) (p < 0.01). Nine of the 17 patients with reversible ST segment shifts who underwent coronary angiography had lesions with morphologic characteristics consistent with atherosclerotic plaque complicated by thrombosis compared with only 2 of 9 patients with T wave changes only (p < 0.05). Plasma concentrations of fibrinopeptide A were markedly elevated in 7 of the 11 patients in whom complex lesions were noted on angiographic examination. Thus, the occurrence of reversible ST segment shifts identifies a group of patients with unstable angina in whom ongoing thrombosis is likely and who may be particularly likely to benefit from antithrombotic therapy.