OBJECTIVE--To describe the natural history of kidney disease in Pima Indians with NIDDM. RESEARCH DESIGN AND METHODS--Review of previous studies describing diabetic kidney disease in this Native-American population and in other populations. RESULTS--NIDDM is the leading cause of renal failure in Pima Indians, among whom the incidence of ESRD is 23 times that of the general U.S. population. The high incidence of NIDDM and its early onset in the Pima undoubtedly contribute to this difference. The incidence of overt nephropathy and ESRD, as a function of diabetes duration, is at least as high in Pima Indians with NIDDM as that reported in other populations with IDDM. Furthermore, nearly all of the excess mortality associated with NIDDM is found in individuals with overt nephropathy. Mild elevations of UAE, which may be present even shortly after the onset of diabetes, predict the development of overt nephropathy in diabetic Pimas. Additional predictors include high blood pressure, level of glycemia, duration of diabetes, family history of diabetic nephropathy, and type of diabetes treatment. CONCLUSIONS--Diabetic kidney disease is a major cause of morbidity and mortality in Pima Indians. The natural history of diabetic kidney disease in this population is similar, in many ways, to the natural history described in individuals with IDDM.