Approximately 80% of the Zuni Indians live in Zuni Pueblo in rural New Mexico. The Zuni are relatively endogamous and differ culturally and ethnically from neighboring tribes. The Zuni Pueblo is experiencing an epidemic of renal disease. The prevalence of end-stage renal disease (ESRD) among the Zuni Indians, adjusted for age and gender, is 6-fold and 21-fold higher than the prevalence rates for Native Americans and European Americans. Almost all Zuni tribal members have a relative with ESRD. This has led to strong public support for renal research. In response, the Zuni community has partnered with the Indian Health Service (IHS), University of New Mexico Health Sciences Center (UNMHSC), Southwest Foundation for Biomedical Research (SFBR), Dialysis Clinic Inc (DCI), and the National Institutes of Health (NIH) to establish a research consortium, the Zuni Kidney Project (ZKP). The goal of the ZKP is to reduce the burden of renal disease in the Zuni community. The ZKP combines traditional, population-based, epidemiologic methods with modern techniques of population genetics. The foundation of the ZKP is a population-based, cross-sectional survey (PBCSS). The PBCSS has 3 specific aims: (1) estimate the prevalence of renal disease in Zuni; (2) assess risk factors for renal disease susceptibility; and (3) identify participants for planned case-control, longitudinal cohort, and family studies designed to identify environmental, familial, and genetic risk factors for the susceptibility and/or progression of renal disease. Preliminary results of the PBCSS confirm that the epidemic of renal disease in Zuni Indians is due to high rates of both diabetic and nondiabetic renal disease. © 2002 by the National Kidney Foundation, Inc.