Recurrence of disease following liver transplantation is emerging as a major area of concern. We retrospectively investigated for evidence of recurrent hepatitis B, hepatitis non-A, non-B (NANB), primary biliary cirrhosis (PBC) and malignancy in 106 transplant patients. Recurrence of hepatitis B was diagnosed in 11 of 14 (79%) patients who survived longer than 2 months posttransplant. The first histologic evidence of recurrence occurred at 4 to 64 weeks posttransplant (mean, 22.2 weeks). In two patients, progression to cirrhosis was documented histologically. Recurrence was diagnosed in three patients transplanted for fulminant hepatic necrosis due to hepatitis B. Administration of hepatitis B vaccine and hepatitis B immunoglobulin was ineffective in preventing recurrence. Recurrence of hepatitis NANB was diagnosed in only two of 23 patients transplanted for hepatitis NANB cirrhosis. Evidence of posttransplant hepatitis was also detected in one of 10 patients transplanted for fulminant hepatitic failure presumably caused by hepatitis NANB. Recurrence of PBC was not diagnosed in any of 15 patients, but the length of follow-up was too limited in most patients to allow definite conclusions to be made. Posttransplant antimitochondrial antibodies titers remained elevated in nine of 11 patients tested. Six of 13 patients transplanted for hepatocellular carcinoma (46%) developed recurrent tumor, and five died. The role of preoperative and postoperative chemotherapy is currently undefined.