To determine whether diabetic patients without known cardiovascular disease have exercise-induced perfusion abnormalities without symptoms, we performed thallium-201 exercise tolerance testing (ETT) on 16 subjects with diabetes mellitus (8 men and 8 women; mean age = 51 ± 2 years). To compare these patients to another group at risk for coronary disease and painless myocardial infarction, 13 hypertensive (7 men and 6 women; mean age = 50 ± 2 years) patients without symptoms of atherosclerotic disease served as controls. Diabetic and hypertensive patients were similar with regard to age, sex, years since diagnosis and other cardiac risk factors. Abnormal exercise thallium testing was more common among diabetic patients (11/16 = 69%; p < 0.05) as compared to hypertensive patients (4/13 = 31%). None of the patients reported chest pain or its equivalent. There was no difference between diabetic and hypertensive subjects in the number of minutes exercised, percentage of maximal heart rate attained or final heart rate achieved. Diabetic subjects as a group had greater evidence of peripheral neuropathy but no abnormality of autonomic nerve function. Using ETT with thallium scintigraphy, diabetic patients without known cardiovascular disease were more likely to have transient myocardial perfusion defects than were hypertensive patients.