Forty-six consecutive adult patients underwent 51 orthotopic liver transplants in a prospective study to evaluate sequential induction with ORTHOCLONE OKT3 (muromonab-CD3), prostaglandin E1, cyclosporine, azathioprine, and methylprednisolone. Infection prophylaxis included preoperative bowel preparation and ganciclovir if cytomegalovirus was diagnosed in either donor or recipient. All rejection episodes were documented by liver biopsy before treatment. Seventy-four percent of patients evaluable beyond 1 year have had no rejection episodes. The retransplant rate was 10%, with a 4% primary nonfunction rate. There was no rejection of grafts that could not be retreated with OKT3. Forty-two percent (5 of 12) of rejection episodes responded to steroid recycling alone. The infection rates for all patients at 1 year were 54% bacterial, 17% fungal, and 22% viral. Three septic deaths were attributed to overimmunosuppression. Two-year patient and graft survival rates were 80% and 72%, respectively. This OKT3 induction protocol results in limited rejection episodes without increasing infections, yielding an acceptably low rate of graft loss.