The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post-transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0-3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post-transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.