Non-insulin-dependent diabetes mellitus is 2-5 times more common in Hispanics than in non-Hispanic whites in the United States. The authors conducted this case-control study in two Colorado counties from 1984 to 1986 to determine whether known risk factors for non-insulin-dependent diabetes mellitus explained the excess incidence in Hispanics. There were 279 subjects with prevalent diabetes and 488 subjects with normal glucose tolerance who were eligible for this analysis. After adjustment for age and sex, results showed that Hispanics were 3.5 times more likely than non-Hispanic whites to have non-insulin-dependent diabetes mellitus (95% confidence interval 2.4-4.9). The excess risks of diabetes associated with body mass index, subscapular and triceps skinfold thickness, family history of diabetes, and income were similar in Hispanics and non-Hispanic whites, after adjustment for age and sex. However, 1-unit increases in subscapular/triceps skinfold ratio and waist/hip ratio were associated with greater increases in risk among non-Hispanic whites than among Hispanics. When risk factors were entered into logistic regression models simultaneously, higher subscapular skinfolds, a higher waist/hip ratio, family history of diabetes, older age, male sex, and lower income were independently associated with non-insulin-dependent diabetes mellitus in both ethnic groups. No association was found with skin reflectance, a marker for Amerindian admixture. While the excess risk of diabetes in Hispanics was reduced, a significant 1.9-fold excess risk in Hispanics remained. Further studies are needed to understand factors contributing to the excess prevalence of diabetes in Hispanic Americans.