Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9% vs 88.8%). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.