The rates of end-stage renal disease are much increased in American Indians, but no longitudinal study of its rates and causes has been undertaken in any tribe. This 15-year study of rates and causes of treated end-stage renal disease in the Navajo, the largest Indian tribe, supplies an important model on which to base projections and plan interventions. Treated end-stage renal disease in Navajos has increased to an age-adjusted incidence 4 times that in whites in the United States. Diabetic nephropathy accounted for 50% of all new cases in 1985, with an incidence 9.6 times that in US whites, and was due entirely to type II disease. Glomerulonephritis caused end-stage renal disease in Navajos at a rate at least 1.8 times that in US whites and afflicted a much younger population. The predominant form was mesangial proliferative glomerulonephritis associated with an immune complex deposition. Renal disease of unknown etiology, which probably includes much silent glomerulonephritis, accounted for 20% of all new cases. The aggregate Navajo population with end-stage renal disease was 9 years younger than its US counterpart. These observations reflect the genesis of the epidemic of diabetic nephropathy afflicting many tribes. Urgent measures are needed to contain this. In addition, the etiology and control of mesangiopathic, immune-complex glomerulonephritis of unusual severity, a previously unrecognized problem, need to be addressed.