Liver transplantation has evolved rapidly from an experimental treatment to universally accepted therapy for end-stage liver disease. Indications for liver transplantation have expanded with the evolution of the procedure to include metabolic,viral, malignant, and acquired liver failure. As long-term liver transplant recipient follow-up data become available, the development of recurrent liver disease within the transplanted allograft is an increasing dilemma. The value of the transplant procedure must be assessed within the context of survival as well as the potential for recurrent disease and the associated need for re-transplantation. This study represents a compilation of data obtained from adult patients undergoing liver transplantation for nonviral, nonmalignant etiologies at the University of California San Francisco and a comparison of our data with other centers. Between February 1988 and January 1997, 654 liver transplants were performed on 623 patients. From this group, 406 recipients were identified as meeting study inclusion criteria: age above 18 years, and transplantation for a nonmalignant, nonviral etiology of liver failure. Indications for liver transplantation included primary biliary cirrhosis (n = 65), primary sclerosing cholangitis (n = 49), autoimmune hepatitis (n = 37),Budd-Chiari syndrome (n = 7), cryptogenic cirrhosis (n = 88),and alcoholic liver disease (n = 160). Mean follow-up within the diagnostic groups ranged from 4.9 to 5.6 years. Evaluation of clinical,immunosuppressive, and pathologic data for each diagnostic group was performed to determine the incidence, time to recurrence, clinical presentation, and sequelae of disease recurrence.