A multicenter, retrospective analysis of 623 liver transplant recipients was performed to define safe and effective cyclosporine doses and blood levels at various times after transplantation. Patient and graft survival were assessed as efficacy parameters, and serum creatinine and cholesterol levels as safety parameters. The mean daily cyclosporine dose was 12.1 mg/kg/d at 1 month posttransplantation and 5.5 mg/kg/d after 1 year. After 4 years, the mean cyclosporine dose was maintained at 4.0 mg/kg/d. Mean cyclosporine blood levels showed a similar trend. Patient and graft survival after 4 years of cyclosporine maintenance therapy were 72% and 67%, respectively. Both serum creatinine and cholesterol levels were stable over the study period, and neither correlated with cyclosporine does. The cumulative incidence of biopsy-proven acute cellular rejection was 59% for early (<6 months) episodes and 21% for late (≤6 months) episodes. Patient and graft survival did not differ significantly between patients experiencing early or late acute rejection episodes and those who did using univariate analysis. The high patient and graft survival, low rejection rates, and lack of significant renal dysfunction or hypercholesterolemia suggest that the cyclosporine doses and blood levels described are safe end therapeutically effective.