Twenty-year protocol biopsies were performed in four cases of renal transplant recipients with grafts that had survived 20 years or more. All four recipients received transplants from their parents, and never had episodes of acute rejection. They were maintained with the conventional immunosuppressive protocol including azathioprine, mizoribine, and prednisolone. Three of them had past history of malignant diseases such as breast cancer and tongue cancer. In spite of fair graft function, the microscopic findings of 20-year protocol biopsy showed various degrees of histological damage; e.g. obsolescence of the glomeruli, glomerulosclerosis, arteriole wall thickening, interstitial fibrosis and tubular atrophy. Although two of the four grafts were functioning with low serum creatinine levels (1.3-1.4 mg dL-1) at 24 years and 26 years following transplantation, respectively, the function of the other two grafts had decreased more than 20 years after transplantation. In the two grafts with decreased function, glomerulosclerosis and arteriole wall thickening tended to be more severe (Banff classification of chronic allograft nephropathy [CAN] grade II and III) at the 20-year protocol biopsy compared with the two well-functioning grafts (CAN grade I and II). We conclude that the protocol biopsies even at 20 years can contribute to predict the fate of renal allografts.