This report reviews the literature and discusses steroid withdrawal after hepatic transplantation. Our experience with steroid withdrawal is highlighted. The hypothesis is that steroid withdrawal from liver transplant recipients is safe and beneficial. A review of the English literature yielded 16 reports with a total of 901 patients (749 adults and 152 children). Most reports were nonrandomized and uncontrolled. Only two reports were randomized, controlled trials; three reports featured early steroid withdrawal (</= 3 months); and one report featured very early steroid withdrawal (14 days). Steroid withdrawal was achieved in approximately 85% of the patients. Acute rejection was not significantly increased by steroid withdrawal; rates were 5% to 14% in uncontrolled trials and 7% versus 7% (late steroid withdrawal v control; P = not significant [NS]) and 4% versus 8% (early steroid withdrawal v control; P = NS) in controlled trials. Acute rejection rates after very early steroid withdrawal (14 days posttransplantation) were 42% to 46%, similar to or less than the 40% to 70% reported for steroid-containing regimens. Chronic rejection was not increased by steroid withdrawal; the rate was 3.9% in one uncontrolled trial and 0% versus 3% (early steroid withdrawal v control; P = NS) in one controlled trial. Patient and graft survival were not adversely affected. Steroid withdrawal was associated with reduced rates and better control of hypertension, reduced total cholesterol levels, reduced rate of posttransplantation diabetes mellitus, improved control of diabetes, and reduced rate of obesity. The aggregate experience with steroid withdrawal suggests it is safe, associated with improvement in several posttransplantation complications, and deserves broader clinical application.