We prospectively evaluated all patients admitted to our coronary care unit during 1993 with ischemic chest pain but without ST-segment elevation on the presenting electrocardiogram, and determined the influence of the extent of ST-segment depression, measured using calipers and blinded to the outcome, on 4-year survival. The presenting symptoms of 367 patients (mean age 64 years) were coded according to the Braunwald classification, 86% being in class IIIB (primary unstable angina with rest angina within 48 hours) and 7.4% in class IIIC (postinfarction angina). Thirty-two patients (8.6%) had myocardial infarction at presentation (defined as a creatine kinase level exceeding twice the reference range within 18 hours). During hospitalization 97% of patients received aspirin, 67% received intravenous heparin, 37% underwent angiography, and 35% underwent revascularization. The vital status of 99% of the patients was determined after a median of 52 months (interquartile range 48 to 55). At follow-up, 88% of patients were taking aspirin, 45% were taking beta blockers, and 50% had undergone revascularization. The survival rate was 70% in patients with > or = 0.5-mm ST-segment depression (53%, 77%, and 82% survival for > or = 2-, 1-, and 0.5-mm ST-segment depression, respectively; p <0.0001). Patients with a normal electrocardiogram had a greater survival rate (94%) than that of patients with 0.5-mm ST-segment depression (82%, p = 0.020), but not significantly different from that of patients with T-wave inversion (84%, p = NS). Independent predictors of mortality (odds ratio [95% confidence interval]) were: age in yearly increments (1.05 [1.03 to 1.06], p = 0.003), revascularization during follow-up (0.40 [0.29 to 0.56], p = 0.006), pulmonary edema (3.45 [2.19 to 5.45], p = 0.007), and ST-segment depression (1.37 [1.20 to 1.55], p = 0.015). Thus, ST-segment depression of > or = 0.5 mm predicts 4-year survival in patients with acute ischemic syndromes.