A 60-year-old man with rheumatiod arthritis, who developed acute reversible renal failure with nephrotic syndrome and tubulointerstitial nephritis in association with multiple-drug therapy, is described. The episode was ascribed to the nonsteroidal anti-inflammatory agent fenbufen, and the patient was reexposed to D-penicillamine within 6 months, reproducing the same renal lesion. There was no evidence of the glomerular lesions characteristically associated with D-penicillamine nephrotoxicity. D-penicillamine was the only drug therapy common to both episodes and it is concluded that it may cause tubulointerstitial nephritis with nephrotic syndrome.