We studied the incidence of biopsy-proven, acute rejection episodes occurring after 1 year posttransplant in cadaver renal allograft recipients. The 328 patients evaluated were given three immunosuppressive drug protocols. Group I (transplanted 9/80-6/84) (n=75) received azathioprine, prednisone (P), and antilympho-blast globulin; group II (transplanted 9/80–6/84) (n=83) received cyclosporine and P; group III (transplanted 7/84-12/86) (n=170) received ALG, AZA, CsA, and P (sequential therapy). The incidence of first acute rejection episodes occurring up to 1 year posttransplant was 55% in group I and 35% in groups II and III. The incidence of late (>1 year) acute rejection episodes was 6.5% in group I, 2.5% in group II, and 9.5% in group III (group II vs. III, P=0.02). In group III, 50% of the late rejections were first, 44% second, and 6% third. The primary etiologies of this increased incidence of late acute rejection may have included subtherapeutic CsA levels and lower P doses. Sequential immunosuppressive therapy has been shown to be advantageous in the first posttransplant year. However, unless adequate immunosuppression is maintained, this approach can be associated with a significantly increased incidence of late acute rejection.