The authors hypothesized that increased socioeconomic status and acculturation of Mexican Americans to mainstream US society would be accompanied by a progressive lessening of obesity and non-insulin-dependent diabetes mellitus. This hypothesis was tested in 1979-1982 in the San Antonio Heart Study, a population-based study of 1,288 Mexican Americans and 929 non-Hispanic whites, aged 25-64 years, randomly selected from three San Antonio neighborhoods: a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb. Socioeconomic status was assessed by the Duncan Socioeconomic Index, a global measure of socioeconomic status based on occupational prestige. Acculturation was assessed by three scales which measure functional integration with mainstream society, value placed on preserving Mexican cultural origin, and attitude toward traditional family structure and sex-role organization. In Mexican-American men, increased acculturation was accompanied by a statistically significant, linear decline in both obesity and diabetes, while socioeconomic status had no significant effect on either outcome. In Mexican-American women, on the other hand, increased acculturation and increased socioeconomic status were accompanied by statistically significant, linear declines in both outcomes. However, the effects of acculturation on obesity and diabetes prevalence in women were stronger than the effects of socioeconomic status. In women, obesity also appeared to be a more important mediator of the relation between socioeconomic status and diabetes than of the relation between acculturation and diabetes. The results of this study suggest that culturally mediated factors exert a more pervasive influence on obesity and diabetes in Mexican Americans than do socioeconomically mediated factors. The influence of socioeconomic status in women, however, cannot be ignored, particularly with regard to obesity.