A total of 504 renal transplants were performed between 1984 and 1993; 408 (81%) were cadaver grafts. This study evaluated the impact of a first acute rejection episode and the severity of the rejection on cadaveric allograft survival. Acute allograft rejection was based on clinical evaluation and confirmed by renal biopsy. Ten patients were excluded from this study due to early patient or graft loss. Patients were divided into Group I (n = 179), who never experienced acute rejection, and Group II (n = 219), who had an acute rejection episode. Group II patients were divided into IIA (n = 140), who had a mild first acute rejection episode treated with methylprednisolone, and IIB (n = 79), who had moderate or severe acute rejection treated with OKT3. The overall 1-, 2-, 3-, and 5-yr actuarial cadaveric renal allograft survival for Group I was 80%, 76%, 74%, and 68%. The corresponding graft survival for Groups IIA and IIB were 75%, 63%, 58%, and 50%; and 79% 71%, 65%, and 53% [p = 0.03 (I vs IIA), p = NS (I vs. IIB and IIA vs IIB)]. A similar pattern of survival was seen in primary kidney allograft recipients. In conclusion, long-term graft survival was superior in patients who never experienced acute rejection compared to those with rejection. Improvements in long-term graft survival can be accomplished in patients with severe rejection with OKT3 treatment resulting in comparable survival to those with mild rejection.