Long-term treatment with corticosteroids after orthotopic liver transplantation (OLT) may cause adverse effects, particularly hypertension, diabetes, and bone disease. The results of steroid withdrawal from long-term immunosuppression in 114 patients after OLT was reviewed. Initial treatment was with corticosteroids, azathioprine, and cyclosporine A in 76.3% and with antithymocyte globulin in 17.5%. Corticosteroids were stopped in 96 patients (84.2%) during mean follow-up of 6.7 +/- 3.9 months, and acute rejection subsequently developed in 8. By comparison 7 of 18 patients, in whom corticosteroids were continued, developed acute rejection. Six of these had received blood group (ABO)-compatible nonidentical grafts. Rates for retransplantation in the steroid withdrawal and nonwithdrawal groups were 4.2% and 22.2%, respectively, and mortality in the two groups was 14.6% and 44.4%, respectively. Azathioprine was not given or withdrawn in 28 patients in the group from which corticosteroids were also withdrawn, with no adverse effect. Diabetes mellitus improved following corticosteroid withdrawal, but there was no improvement in hypertension. We conclude that corticosteroids can be safely withdrawn in the majority of patients after OLT.