Since 1989, the immunosuppressive regimen used in all heart transplant patients at our center has consisted of (i) cyclosporine induction therapy (pretransplant p.o. 2-6 mg/kg depending on serum creatinine level, with immediate post-transplant i.v. therapy at 1-3 mg/h until p.o. therapy alone maintains a whole blood trough level of 300 ng/ml by RIA); (ii) azathioprine (2.5 mg/kg/d i.v./p.o.); (iii) methylprednisolone i.v. for 24 h and then prednisone p.o. at 1 mg/kg/d, tapering to 0.1 mg/kg/d at 1 yr. No prophylactic cytolytic agents (ALG, OKT3) were given. One hundred consecutive patients have been followed for periods of 4-56 months (mean 27 months). The incidence of acute rejection requiring increased therapy was 24%, with only 7% requiring i.v. steroids, 2 of whom (2%) also required ALG and/or OKT3, and with 17% requiring increased oral immunosuppression alone. Mean creatinine levels (mg/dl) were 1.3 pre-transplant, 1.4 on d 7, 1.5 at 30 d, and 1.8 after 2 yr. Only 1 patient required temporary hemodialysis. Survival was 98% at 30 d, 94% at 1 yr, and 92% at 2 yr. We conclude that cyclosporine induction therapy with steroids and azathioprine without any cytolytic agent results in a low incidence of acute rejection without jeopardizing renal function.