The association between fasting plasma insulin level and coronary heart disease (CHD) was studied in 909 non-insulin-dependent diabetic (NIDDM) patients, aged 45-64 years, and in 1,373 nondiabetic control subjects. Both diabetic and nondiabetic subjects with various manifestations of CHD had higher plasma insulin levels than did subjects free of CHD. By plasma insulin quintiles formed according to values in nondiabetic subjects, the age-adjusted prevalence of CHD defined by symptoms and/or electrocardiographic changes in diabetic men was 48.2% in quintiles I + II (lowest), 54.8% in quintiles III + IV, and 65.7% in quintile V (highest) (p = 0.006). The respective prevalences in diabetic women were 53.5%, 59.1%, and 73.3% (p = 0.004); in nondiabetic men, 28.1%, 33.7%, and 43.3%, respectively (p = 0.016); and in nondiabetic women, 28.1%, 34.9%, and 44.3%, respectively (p = 0.007). An essentially similar association was observed between plasma insulin level and definite or possible myocardial infarction (MI). In diabetic subjects, a positive association between plasma insulin level and CHD manifestations was also found when insulin strata were formed using quintile cutoff points determined separately from diabetic subjects. The association between plasma insulin level and the prevalence of CHD or MI disappeared or was weaker, especially in men, when adjustment was made for body mass index, hypertension, and triglyceride or high density lipoprotein (HDL) cholesterol level. The association between high plasma insulin level and CHD was significant in diabetic subjects with a body mass index greater than 27 kg/m2 but not in those diabetics with a body mass index less than or equal to 27 kg/m2. A significant clustering of hypertension, high triglyceride values, and low HDL cholesterol levels was observed in diabetic subjects in the highest insulin quintiles. The results suggest that hyperinsulinemia is an indicator of CHD in both NIDDM patients and nondiabetic subjects. Hyperinsulinemia may be directly atherogenic, but it is more probable that hyperinsulinemia reflects insulin resistance, which may be a factor enhancing atherogenesis by causing adverse changes in many CHD risk factors.