Cyclosporin A combined with prednisone was compared with standard immunosuppressive therapy (antilymphoblast globulin, prednisone, and azathioprine) in a prospective randomized trial of 100 mismatched, living related donor and cadaveric renal transplants. The results demonstrated cyclosporin A plus prednisone to be an effective immunosuppressive regimen for renal transplantation. The actuarial graft survival at 1 year was 93% for patients treated with cyclosporin A and 81% for patients treated with conventional immunosuppression. Patient survival was 98% for the cyclosporin A group and 100% for the conventional group. Cyclosporin A-treated patients had fewer rejection episodes and fewer infections complications including a marked decrease in the incidence of posttransplant cytomegalovirus infection. The side effects of cyclosporin A were mild, but nephrotoxicity caused by cyclosporin A was frequent and significant. Nephrotoxicity was reversible and managed by decreasing the daily cyclosporin A dose. It is concluded that the combination of cyclosporin A plus prednisone provides an excellent alternate immunosuppressive regimen for renal transplants as compared with conventional therapy. The consequences of long-term administration of cyclosporin A are at present unknown.