Interstitial periodic acid-Schiff positive deposits of amorphous or fibrillar material were observed in 32% of kidneys with a variety of tubulointerstitial diseases, including medullary cystic disease (60%), chronic pyelonephritis (20%), and hydronephrosis (33%). Immunofluorescent staining for Tamm-Horsfall protein showed interstitial localization of this protein which was identical in distribution, shape, size, and fine detail with the periodic acid-Schiff positive deposits. The deposits appeared to originate from disrupted tubules and were sometimes surrounded by inflammatory infiltrate. The intrarenal localization of Tamm-Horsfall protein outside of distal tubules in pathologic states indicates that this protein may have a role in the pathogenesis of renal disease.