Abstract In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control Subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 ± 1.1% (mean ± SEM) in control subjects, 3.1 ± 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 ± 1.4% (p <0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (<50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p <0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by <5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination. In patients with IDDM, the respective increase was from 43% to 52% (p = NS, compared With control subjects), and in patients with NIDDM from 53% to 73% (p = NS). Duration and metabolic control of diabetes, presence of diabetic complications, and LVEF at rest or during exercise at baseline did not differ in either diabetic group between the patients who had normal or abnormal LVEF at rest or in response to exercise at follow-up examination. No study subject experienced clinical heart failure during follow-up, but 7% of control subjects, 37% of patients (p <0.001) with IDDM, and 34% of patients (p <0.01) with NIDDM had coronary artery disease at follow-up examination. In conclusion, LVEF at rest deteriorated significantly during 4-year follow-up in patients with NIDDM but not in patients with IDDM. A high prevalence of subclinical LV systolic dysfunction became evident both in patients with IDDM and patients with NIDDM as an abnormal LVEF response to exercise both at baseline and follow-up examinations.