Southern-born black and white Americans suffered severe economic deprivations during the first half of the twentieth century. We hypothesized that these conditions increased their risks of dying from cancer, diabetes, heart and cerebrovascular diseases. Mortality files for the years 1979 to 1991 for the United States and a specially constructed US Census population file were used to calculate age-specific and age-adjusted death rates for black and white males and females by region of birth and region of residence at time of death. Death rates of Southern-born populations were compared to the death rates of populations born in the Northeast, Midwest and West. The Southern-born effect was manifested in higher death rates from cancer, diabetes, heart and cerebrovascular diseases for both black and white populations. The Southern-born effect is larger than black/white differences for cancer and of similar magnitude for heart and cerebrovascular diseases. Follow-up investigations are needed to isolate key elements of the Southernborn effect that can be addressed through interventions.