Plasma lipids, lipoproteins, and apolipoproteins were measured in 123 female and 57 male Mvskoke Indians, a population of American Indians with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Dietary patterns were assessed with a food-frequency questionnaire. There were no differences in total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), apolipoproteins A-I or B in female Indians with and without diabetes. In males with diabetes, however, LDL-C was lower. Triglyceride and fasting plasma glucose were higher in subjects with diabetes. Total cholesterol and LDL-C were lower and HDL-C was higher than age and sex-matched Lipid Research Clinics values, especially for subjects with diabetes. This is surprising given that the diet of Mvskoke Indians contains foods high in total fat, saturated fatty acids, and cholesterol. We may explain, in part, the low incidence of coronary heart disease in this population.