Resting ST segment depression has been identified as a marker for adverse cardiac events in patients with and without known coronary artery disease. To correlate this with exercise testing, coronary angiography, and how it impacts on long-term prognosis, a retrospective study was performed on 476 patients, of whom 223 had no clinical or electrocardiographic evidence of prior myocardial infarction while 253 were survivors of an infarction. All patients performed a standard exercise test and underwent diagnostic coronary angiography within an average of 32 days of their exercise test (range 0 to 90 days). Exclusions were women, those with left bundle branch block, left ventricular hypertrophy, use of digoxin, previous revascularization procedures, or significant valvular or congenital heart disease. Long-term follow-up was carried out for an average of 45 months (+/- 17). Of the patients without prior infarction, 23 (10%) had persistent resting ST segment depression, and of those with a prior history of infarction, 37 (15%) also had resting ST segment depression. Patients with resting ST segment depression and no prior myocardial infarction had a higher prevalence of severe coronary disease (three-vessel and/or left main) (30%) than those without resting ST segment depression (16%) (95% confidence interval [CI] for observed difference -5.0% to 33.9%, p = 0.12). The criterion of greater than or equal to 2 mm of additional exercise-induced ST segment depression was a particularly useful marker in these patients for the diagnosis of any coronary disease (likelihood ratio 3.35, 95% CI 0.56 to 19.93, p = 0.06). Patients with resting ST segment depression and a prior myocardial infarction had a 2.5 times higher prevalence of severe coronary artery disease compared with patients without resting ST segment depression (43% versus 17% prevalence, respectively, 95% CI for observed difference 9.38% to 42.8%, p less than 0.001) and also had larger left ventricles postinfarction (left ventricular end-diastolic volume index 102 ml/m2 compared with 96 ml/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)