To assess the relations of electrocardiographic measures of ischemia with the development of adverse coronary events, 86 patients with stable coronary artery disease and positive exercise tests for myocardial ischemia underwent ambulatory monitoring of the electrocardiogram. Monitoring was performed after withdrawal of antianginal medications, and prospective follow-up was obtained on routine medical care as prescribed by physicians who were unaware of monitor results. Forty-nine patients (57%) had a total of 426 episodes of ST segment depression; only 60 episodes (14%) were associated with symptoms of angina or an equivalent. During a mean follow-up of 12.5 +/- 7.5 months, there were two cardiac deaths, four myocardial infarctions, four hospitalizations for unstable angina, and 11 revascularization procedures required for new or worsening symptoms in 15 patients. All but one of these events (a hospitalization for unstable angina) occurred in the group of patients with ST segment depression on monitoring (p = 0.003). In multivariate analysis controlling for age, sex, and clinical descriptions of angina, the presence of ischemia on ambulatory monitoring was a significant predictor of outcome, while exercise test characteristics were not. Therefore, ischemia detected by ambulatory monitoring was common in patients with stable symptoms of coronary artery disease, and its presence identified a high-risk group for the development of subsequent unfavorable outcomes while on routine medical therapies.