1. According to a recent hypothesis, based on similarities between chronic graft versus host disease and primary biliary cirrhosis (PBC), immune reactions against histocompatibility (HLA) antigens-6-be responsible for the bile duct damage and extrahepatic lesions of PBC. 2. Previous studies have demonstrated autoimmune reactions in PBC against normal human biliary tract antigens. To equate these findings with the above hypothesis, it has been suggested that the biliary antigens are related to the HLA system and, in the present study, this possibility has been investigated by: (a) using preparations of the biliary antigens to inhibit the lymphocytotoxic activity of standard HLA-typing sera against normal lymphocytes, and (b) employing guinea-pig antisera raised against the biliary antigens as ‘typing reagents’ in the lymphocytotoxicity test to determine whether these antisera recognize HLA components on the surfaces of normal lymphocytes. 3. No inhibition by the biliary antigens of the reaction of two standard typing sera against T-and B-lymphocytes from two normal healthy donors (covering nine HLA-A, -B, -C and three HLA-DR loci antigens) was observed. Conversely, the guinea-pig antisera showed no reaction against these lymphocytes. 4. The results suggest that the biliary tract antigens are probably not related to ‘common’ antigenic determinants associated with the HLA system.