OKT3 monoclonal anti-T cell antibody was used during the first 2 weeks following cadaveric renal transplantation to prevent rejection. When compared with a control group receiving triple immunosuppression with cyclosporine, azathioprine, and prednisone, the OKT3, azathioprine, and prednisone group had significantly fewer acute rejections during the first month (6% v 50%; P less than 0.01), and the mean time of onset of the first rejection was significantly delayed (day 47 v day 8; P less than 0.01) in the OKT3 prophylaxis group. OKT3 was administered intraoperatively safely and without complications on the day of transplantation. The well-reported first dose reaction to OKT3 was similar in these patients when compared with patients receiving OKT3 for treatment of rejection. Anti-OKT3 antibody development occurred in half of the patients receiving OKT3, and did not prevent the subsequent use of OKT3 in these patients, whose rejections following OKT3 prophylaxis were steroid reversible. There were no deaths among the patients receiving prophylactic OKT3, and during a 15-month follow-up, only three of 34 kidneys were lost for any reason. In addition to its use for primary and steroid-resistant rejection, OKT3 may be useful early after transplantation to prevent rejection.