The prevalence and cineangiographic correlates of exercise-induced inversion of U waves were studied in 248 patients. Exercise-induced U-wave inversion was observed in 36 patients (15%), of whom 35 had greater than or equal to 75% stenosis in one or more of the major coronary arteries. The proximal left anterior descending or left main coronary artery was involved in 33 of these patients, including 24 patients with no electrocardiographic evidence of anterior myocardial infarction. Exercise-induced U-wave inversion was observed in the absence of an abnormal resting 12-lead ECG. Only one of the 82 patients (1.2%) without significant coronary artery disease demonstrated exercise-induced U-wave inversion, and this patient had a primary cardiomyopathy. We conclude that exercise-induced inversion of the U-wave is highly predictiveof significant coronary artery disease and, more specifically, of disease of the proximal left anterior descending coronary artery.