The relationship of renal disease to carbohydrate tolerance was examined in the Pima, who are American Indians with a high prevalence of diabetes mellitus. Glucose tolerance, serum creatinine level and urine protein concentration were measured in 1,716 subjects aged fifteen and over, of whom 404 were diabetic. Histologic information was obtained by reviewing autopsy material from forty-three diabetics and sixty-two nondiabetics. Over 22 per cent of the diabetics and less than 7 per cent of the nondiabetics had proteinuria (p < 0.001). Severe proteinuria aid elevated serum creatinine levels were, respectively, fifteen and nine times more common in the diabetics (p < 0.001). Both the frequency and severity of renal disease increased with duration of diabetes in subjects who were under age sixty-five when examined or when the disease was diagnosed. Above age sixty-five the prevalence of proteinuria was high in all duration groups. At autopsy, 65 per cent of the diabetics had diffuse glomerulosclerosis. Nodular glomerulosclerosis was found in 56 per cent of the diabetics and in none of the nondiabetics. Arteriolar lesions were also significantly more common in the diabetics. Pyelonephritis was found in 16 per cent of the diabetics and 5 per cent of the nondiabetics; other forms of renal disease were rare in both groups. Diabetic nephropathy, similar in its clinical and histologic characteristics to that described in other populations, is the predominant form of kidney disease in the Pima Indians, making this population ideal for study of the development and course of diabetic renal disease.