A controlled trial was carried out in 209 primary cadaveric renal transplants to compare the effects of cyclosporine and steroids (double therapy) with those of cyclosporine in lower initial dose, azathioprine, and steroids (triple therapy). Patients have been followed 1-36 months since transplantation. Actuarial two-year graft survival (double 74%, triple 76%) and two-year patient survival (double 90%, triple 93%) were similar for both groups. Further analysis of particular risk factors including age, diabetes, HLA matching, acute renal failure, and use of sequential Minnesota antilymphocyte globulin in patients with delayed graft function also showed similar outcomes with both immunosuppressive regimens. Initial hospitalization time, rate of rejection, incidence of serious infection, and rate of rehospitalization were not different. Mean CsA doses and mean trough whole-blood levels were higher in double-therapy patients at hospital discharge but not by three months posttransplant. There were no differences between the two groups in iothalamate clearance at any time. Hypertension was more frequent six months posttransplant in the triple-therapy group (p less than 0.05). Thus, similar results were obtained with both regimens, and except for hypertension no regimen appeared to have increased side effects up to three years posttransplant.