With usual immunosuppression, the incidence of acute rejection after liver transplantation is higher than 60% in most series. The aim of this prospective study was to assess the value of a powerful initial immunosuppression on acute rejection, mortality and morbidity. REGIMEN. Group 1: patients with normal postoperative renal function (serum creatinaemia < 150 mumol/L) received cyclosporine from day 1 to day 15 by continuous i.v. infusion to reach a whole blood level of 400 to 500 ng/mL; after day 15, cyclosporine was reduced. Group 2: in cases of postoperative renal failure (serum creatinine > or = 150 mumol/L), anti-thymocyte globulins were used for 10 days; cyclosporine was introduced after recovery of renal failure at usual doses. In addition, all patients received steroids and azathioprine according to usual regimens. RESULTS. From January 1989 to June 1992, 60 cases were studied in 59 patients: 45 (75%) entered group 1 and 15 (25%) entered group 2. In group 1, there were 11 acute rejection episodes (24%) and one postoperative death at three months (2.3%). In group 2, two early deaths (within 5 days) were excluded from the study of rejection. Among the 13 remaining cases, there were three episodes of acute rejection (23%) and one hospital death at three months. Overall, there were 14 episodes of acute rejection (24%), 12 of which were steroid-responsive (86%), no chronic rejection, a usual rate of infections (57%), one retransplantation (1.7%) and a hospital mortality of 6.8% (4 of 59 cases). One year survival was 78%, with 5 of 7 late deaths due to recurrent cancer. CONCLUSIONS. Our results suggest that, after liver transplantation, a) high initial cyclosporine dose in patients with normal postoperative renal function is associated with reduced incidence and severity of acute rejection without increased mortality and morbidity, b) antithymocyte globulins are an efficient alternative to cyclosporine in patients with postoperative acute renal failure and saves OKT3 for the treatment of steroid-resistant rejection.