A retrospective histopathologic review of all pathologic specimens from 394 adult liver transplant patients was undertaken with clinical correlation to determine if primary biliary cirrhosis has affected the posttrans-plant course compared to all other indications for liver transplantation and if recurrent primary biliary cirrhosis has occurred after liver transplantation. We also compared the histopathologic features seen in native livers with primary biliary cirrhosis to failed allografts with chronic rejection. One hundred six of the 394 adult patients transplanted during this time (1981 to July, 1986) fulfilled clinicopathologic criteria for a diagnosis of primary biliary cirrhosis. Neither the incidence nor any qualitative pathologic feature of histologically documented acute cellular rejection differentiated subjects transplanted for primary biliary cirrhosis vs. other diseases. No correlation between the titers of antimitochon-drial antibody and the presence of posttransplant hepatic dysfunction based on liver enzyme profiles or the development of chronic rejection was seen in patients transplanted for primary biliary cirrhosis. Minor differences noted in the posttransplant course of primary biliary cirrhosis patients as compared to other conditions (higher incidence of chronic rejection as a cause of graft failure) was seen, but this did not significantly affect graft or patient survival. Recurrent primary biliary cirrhosis could not be diagnosed with certainty in any patient. A comparison of failed chronically rejected allografts vs. native hepatectomies obtained from patients with primary biliary cirrhosis revealed the presence of chronic obliterative vasculopathy, centrilobular cholestasis, and lack of granulomas, cirrhosis, cholan-giolar proliferation, copper-associated protein deposition and Mallory's hyalin in specimens with chronic rejection. In contrast, livers removed from patients with primary biliary cirrhosis demonstrated a mild vasculopathy, cirrhosis, granulomas, copper-associated protein deposition, Mallory's hyalin and periportal cholestasis. Both conditions demonstrated a nonsuppurative destructive cholangitis with bile duct paucity.