The clinical and histological spectrum of renal allograft rejection occurring in the early posttransplant period is well described, but there is not much information with regard to the nature of graft rejection occurring in the long-term survivors of renal transplantation. In this study, we analyzed the incidence, clinical and histological data, and outcome of graft rejection in 69 patients who survived with a functioning kidney for 10 years or longer. In this second decade, during a mean follow-up of 3 years (0.1-9.7 years), 15 patients (22%) developed 20 late rejections. Two of them received living-donor transplants and 13 received cadaver kidneys. Only 8 of these rejections (40%) were associated with abnormal clinical findings; the other 12 (60%) were asymptomatic and were detected on the basis of an unexplained deterioration in graft function. The diagnosis was made on clinical grounds in 10 cases and the other 10 were confirmed by renal histology: acute cellular rejection 1, acute cellular rejection superimposed on chronic rejection 4, and chronic rejection only 5. Thirteen acute rejections in 8 patients were treated with high-dose steroids. Of these, 6 (46%) responded fully, 4 (31%) responded partially, and 3 (23%) did not respond. Seven patients with chronic rejection were not treated. Of these, 5 have returned to dialysis within a mean period of 8 months and one patient died of hepatic failure. Our data suggest that acute reversible graft rejections can occur even after 10 years following renal transplantation. It is therefore essential to continue the maintenance immunosuppressive therapy and monitor the clinical and renal functional data at regular intervals in long-term survivors of renal transplantation.