The effect of cyproheptadine, a potent platelet deaggregator, was investigated in rats bearing renal allografts. Thirty-three bilaterally nephrectomized LEW rats received orthotopic transplants of a (LEW X BN)F-1 kidney. Fourteen rats were treated with cyproheptadine, 1.5 mg/kg i.m. daily, for 60 days after transplantation; the remaining animals served as controls. The median allograft survival time in the cyproheptadine group was prolonged to 64 days compared to 12 days in the untreated group (P less than 0.005). In the cyproheptadine group the blood urea nitrogen rose to over 150 mg/100 ml 1 week after transplantation, fell to 80-120 mg/100 ml, and then rose steadily from the day after transplantation until the death of the animals. Despite prolonged survival, cyproheptadine-treated animals usually showed the histological findings of acute and chronic renal rejection. Cyproheptadine may be a useful adjunct to immunosuppression in the management of human renal allotransplantation.