We report a 35-year-old man with adult polycystic kidney disease (APKD) that developed nephrotic syndrome accompanied by a rapid worsening of renal function. Histologic examination showed marked tubulointerstitial chronic abnormalities and focal glomerulosclerosis (FGS) lesions in 24% of the glomeruli. With captopril, an angiotensin-converting enzyme inhibitor, proteinuria showed a clear decrease, but renal function continued to deteriorate. No other cases of nephrotic-range proteinuria were detected among 65 APKD patients with renal insufficiency. Histologic examination of an other 12 kidneys removed from patients with APKD showed striking interstitial lesions, most of the glomeruli being normal. However, those patients with higher amounts of proteinuria had more glomeruli (14-32%) with FGS lesions.