To assess the geographical patterns of end-stage renal disease (ESRD) incidence and to identify the risk factors on the regional differences, the authors conducted an ecological study on incidence of ESRD and related risk factors in the 46 counties of South Carolina (SC). Age and gender adjusted, race specific incidence rates for each county in SC were calculated for the 11,346 ESRD patients of all ages who registered in the United States Renal Data Systems Network 6 from 1990 to 1999. County level exposure measures on population physician density, hospitalization rates of diabetes and hypertension, per capita income, percent college degree, and percent below poverty were evaluated. There was a significant increase in mean incidence rates of ESRD from 1990 to 1999 in SC (p<0.0001). The incidence rates were consistently higher in rural than in urban counties. Population physician density (relative risk (RR) 0.49, 95% confidence interval (95%Cl, 0.41-0.58) and rural residence (adjusted RR 1.66, 95%Cl 1.59-1.74) were significantly associated with ESRD incidence. The strong relationship between ESRD and physician density suggests that access to adequate treatment of diabetes and hypertension is of paramount importance for ESRD prevention, and has important public policy implications.