The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post–glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (SI), glucose effectiveness (SG), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n = 288), Hispanics (n = 363), and non-Hispanic whites (n = 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower SI than non-Hispanic whites. No ethnic difference was observed in SG. After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower SI, than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in SI or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to havehigher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between SI and upper body adiposity (waist-to-hip ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics, the greater insulin resistance may be due to greater adiposity and other behavioral factors.