The failure of exercise-induced ST segment depression to consistently predict prognosis in patients after myocardial infarction could be a result of population differences and the rest electrocardiogram (ECG). These hypotheses were tested by studying 198 veterans who survived a myocardial infarction, underwent a submaximal predischarge treadmill exercise test and were followed up for cardiac events for 2 years. During the 2 years, 29 deaths, 19 reinfarctions and 28 revascularization procedures were documented. The prevalence of death or reinfarction was two times higher in patients who had exercise-induced ST depression than in patients who did not. However, in the 55 patients without Q waves, the risk increased to 11 times for an abnormal ST response. These findings suggest that exercise-induced ST depression only predicts high risk in patients after myocardial infarction whose ECG at rest does not exhibit Q waves and that differences in the prevalence of rest ECG patterns are the most likely explanation for the failure of agreement among prior studies.