The influence of changes in sociocultural status on obesity, arterial blood pressure, and depression was examined in a cohort of 81 Seri Indians living in two communities in Sonora, Mexico. Residents of the less acculturated and modernized community, Desemboque, exhibited significantly higher waist circumference and prevalence of obesity than did residents of the more acculturated and modernized community of Punta Chueca. The prevalence of obesity was also significantly associated with low levels of acculturation and modernization, while the prevalence of clinically significant depressive symptoms was associated with low levels of modernization and household income. Lifestyle incongruity was a significant independent risk factor for body mass index and depressive symptom scores but not for arterial blood pressure. The results support the notion of a curvilinear relationship between health status and sociocultural change in which health status initially declines with increasing lifestyle incongruity but eventually improves with increasing acculturation, modernization, and income.