Interstitial deposits of periodic acid-Schiff positive fibrillar material have been detected in a variety of diseases associated with tubulointerstitial pathology. This material has been shown to be Tamm-Horsfall protein by immunofluorescent, immunochemical, and electron microscopic studies. Prospective evaluation of 133 kidneys revealed deposits in 11 per cent. These deposits included medullary cystic disease (50 per cent), obstructive uropathy and vesicoureteral reflux (21 per cent), and tubulointerstitial disease (29 per cent). Tamm-Horsfall protein was also detected in Bowman's space in four cases of obstructive uropathy. It is proposed that these deposits result from severe tubular damage with release of Tamm-Horsfall protein from its normal intracellular and intralumenal locations into the renal interstitium. We speculate that the intersitial deposition of this sequestered protein may result in a continued inflammatory response and progressive renal damage.