We examined the expression of blood group antigens of the ABO, Lewis and Kell antigen systems using monoclonal antibodies and immunohistochemical study on 42 liver allograft specimens from 33 patients who underwent liver transplantation between 1986 and 1991 to learn whether altered blood group antigen expression might have a bearing on the immunopathogenesis of transplant rejection. Specimens were obtained at intervals of 0 days to 3 yr after transplant; they yielded the following histological diagnoses; time zero (n = 4), acute rejection (n = 4), pure cholestasis (n = 4), biliary obstruction (n = 4), early chronic rejection (n = 4), end-stage chronic rejection (n = 15) and miscellaneous late posttransplant biopsies (n = 7). Aberrant expression of blood group antigens was observed in 5 of 15 patients with chronic rejection. Two transplants into the same group O patient showed aberrant expression of AB antigens on hepatocytes, with a canalicular pattern, in group O-transplanted livers. In all three cases in which a group O liver was transplanted into a group A recipient and histological signs of chronic rejection were present, antibody staining showed acquisition of recipient blood phenotype by the donor liver bile ducts, endothelium or both. Aberrant expression of ABO antigens was seen only in chronic rejection. In seven cases we noted canalicular staining of periportal hepatocytes with the Lewis antibodies, normally confined to ducts and ductules. This was associated with severe cholestasis in six of the seven cases and may have represented early ductular metaplasia. These changes in carbohydrate cell surface phenotype may play a role in regulation of hepatic allograft susceptibility to immune-mediated damage.