Chronic tubulointerstitial renal disease and villous atrophy of the small intestine occurred in two first cousins. Both had protracted diarrhea with malabsorption and died despite intensive parenteral alimentation. In one patient signs of generalized proximal tubular dysfunction developed, followed by nephrotic syndrome and progressive renal insufficiency. A renal biopsy specimen disclosed severe tubulointerstitial disease and membranous glomerulopathy. In this patient, circulating immune complexes were detected and granular deposits of IgG and C3 were seen in the intestinal epithelial cells by direct immunofluorescence. Antiintestinal antibodies (IgG class) were demonstrated by indirect immunofluorescence. The other patient had interstitial nephritis but no glomerular abnormality. On direct immunofluorescence, both patients had confluent granular staining of the renal tubular basement membranes. These immunopathologic studies suggest a common immunologic mechanism in the pathogenesis of the renal and gastrointestinal disorders in these infants.