To identify factors associated with diabetes mellitus and to determine whether racial differences in these factors, especially socioeconomic status, explain the high prevalence of diabetes among African-Americans, we performed a cross-sectional study using a population-based, representative sample from three US communities. The participants comprised 975 white and 418 African-American adults, aged 35 to 54 years. The main outcome variable was the presence of diabetes defined by either self-report or abnormal results on the oral glucose tolerance test (serum glucose level > 10.0 mmol/L (180 mg/dL) 1 hour after 50-g oral glucose dose). Compared to their white counterparts, African-American participants were more overweight, displayed greater central adiposity, and had lower socioeconomic status. Diabetes was over twice as prevalent among African-Americans (10.3%) as compared to whites (4.6%; odds ratio (OR) = 2.38; 95% confidence interval (95% CI): 1.50, 3.75; P = 0.0001). After adjustments for racial differences in age, socioeconomic status, overweight, and central adiposity, African-Americans remained over twice as likely to have diabetes compared to whites (OR = 2.35; 95% CI: 1.49, 3.73; P = 0.0003). The excess prevalence of diabetes in African-Americans was greatest in individuals of low socioeconomic status (OR = 4.09) and least among individuals of high socioeconomic status (OR = 1.90; P < 0.001 for trend). Racial differences in obesity and socioeconomic status do not appear to explain fully the higher prevalence of diabetes among African-Americans. African-American race seems to be a strong, independent risk factor for diabetes, especially among individuals of low socioeconomic status.