Myocardial free fatty acid metabolism and left ventricular function were evaluated in 15 middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 8 healthy control subjects. The study subjects had no evidence of coronary heart disease on the basis of clinical history, exercise ECG or myocardial perfusion scintigraphy. During peak exercise, iodine-123 hepatadecanoic acid (HDA) was intravenously injected. Myocardial activity distribution of 123I-HDA was measured 10, 30, and 50 min after exercise using single-photon emission tomography (SPET); and then further corrected by free 123I-iodine. Venous blood samples were drawn for detecting the plasma activity of 123I. The net extraction of 123I-HDA into the myocardium was obtained by dividing the corrected tissue 123I concentration by the integral of the plasma time activity curve. The net extraction was 0.40 +/- 0.06 min-1 (mean +/- SD) patients with NIDDM and 0.38 +/- 0.06 min-1 in control subjects (P greater than 0.1), respectively. The faster elimination rate of 123I-HDA was found in patients with NIDDM (0.029 +/- 0.008 min-1) than in control subjects (0.022 +/- 0.004 min-1; P less than 0.01). There was no statistically significant difference in left ventricular ejection fraction (LVEF) at rest between patients with NIDDM (53 +/- 9%) and control subjects (56 +/- 2%), whereas the increase of LVEF during exercise remained lower in patients with NIDDM (3.4 +/- 8.2%) than in control subjects (11.8 +/- 5.8%; P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)