Because absorption of cyclosporine (CyA) given orally immediately after liver transplantation is unreliable, the drug is usually given intravenously until external biliary drainage is discontinued. Intravenous CyA, however, is associated with serious side effects, making its use potentially hazardous. We report the results of a new strategy in which we used oral CyA exclusively and refed bile to enhance oral CyA absorption. Thirty-two liver transplant recipients with indwelling T tubes were studied. All were given sequential quadruple drug immunosuppression with antilymphoblast globulin, azathioprine, and steroids. Oral CyA and refeeding of bile was started when renal function was stable. By the second posttransplant week, satisfactory CyA levels were achieved, and antilymphoblast globulin therapy was stopped. There were significant associations between oral CyA dose and CyA level and between quantity of refed bile and CyA level (p less than 0.001). CyA dose and quantity of bile refed were covariates, however, and in multiple regression analysis, only the quantity of refed bile was significant (p = 0.001). CyA levels did not correlate with rejection. The incidence of rejection was 63%. At a mean follow-up of 9 months, 28/32 (88%) patients were alive, and actuarial 1-year patient survival was 84%. Current graft and renal function are excellent (serum bilirubin, 1.0 +/- 0.1 mg/dl; serum creatinine, 1.2 +/- 0.1 mg/dl). We conclude that intravenous CyA can be avoided in virtually all liver-transplant recipients by administration of oral CyA with bile in the early posttransplant period.