Zuni is a Pueblo Indian village having more than a sixfold greater incidence of nondiabetic end-stage renal disease than the rest of the United States. Renal biopsy specimens from 44 patients with nondiabetic renal disease were subdivided into two groups. In group 1, 21 patients with asymptomatic microscopic hematuria revealed a mild mesangiopathic glomerulonephritis in 18 cases. The predominantly staining immunoglobulin was IgM in ten specimens and IgA in eight specimens. In group 2, 23 patients with symptomatic renal disease presented with nephrotic range proteinuria (11), renal insufficiency (eight), and hypertension (four). A mesangiopathic glomerulonephritis was diagnosed in 16 cases, and in 11 was IgA predominant. Three cases of membranoproliferative glomerulonephritis occurred in group 2. Five cases revealed focal glomerulosclerosis without immune deposits (three in group 1 and two in group 2). More than half (57%) of the patients undergoing biopsy were related. Cases of symptomatic nondiabetic renal disease showed a significant tendency to cluster among the members of four families, suggesting a hereditary influence in the pathogenesis of immune-mediated glomerulonephritis in the Zuni.