A total 166 first cadaveric renal allograft recipients were randomly assigned to receive either rabbit antithymocyte serum (RATS) (n = 83) or OKT3 (n = 83) for 10 to 14 days after transplant as prophylaxis against rejection. Both groups were similar with respect to age, sex, donor age, diabetes, time on dialysis, panel-reactive antibody, HLA matching, and transfusion before transplantation. All patients were followed for 1 year after transplantation. A comparison of the rejection rates between the 2 groups of patients showed that patients receiving OKT3 had a rate of first rejection 1.87 times higher than those receiving RATS (95% confidence interval 1.18-2.8, P = 0.007). Twenty-five steroid-resistant rejections occurred in OKT3-treated patients as compared with 12 in the RATS-treated group (P < 0.05). There was no significant difference in early or late renal function between the 2 groups of patients. Actuarial 1-year graft survival for the RATS group was 78% and for the OKT3 group, 80.7% (P = NS). Actuarial 1-year patient survival was similar: 89.5% in the RATS group and 94.6% in the OKT3 group (P = NS). Total hospitalization time was 29.8 +/- 19.9 days for RATS vs. 39.5 +/- 22.1 days for those treated with OKT3 (P < 0.006). A number of infections were observed but there were no significant differences between the groups. We conclude that RATS provides better prophylaxis than OKT3 in first cadaveric renal transplants because it is associated with fewer rejection episodes, less hospitalization, and no additional morbidity or mortality.