BACKGROUND The purpose of this study was to investigate lymphocyte adhesion to Kupffer cells as a component of an immune-mediated mechanism for halothane hepatitis. METHODS Kupffer cells were isolated from guinea pigs exposed to 1.0% halothane/40% oxygen and cultured with various synthetic antigens (trifluoroacetyl-protein adducts or hepatocyte homogenate from halothane-exposed animals). Latex beads were also added to Kupffer cell cultures to determine if activation of these macrophages would result in an increased cellular adhesion. Lymphocytes which had been surfaced-labeled with biotin were added to treated Kupffer cells, and lymphocyte adhesion was determined using a streptavidin-peroxidase reagent for colorimetric detection. RESULTS Trifluoroacetyl-lysine, trifluoroacetyl-rabbit albumin or guinea pig albumin did not induce lymphocyte adhesion. Latex beads also had no effect on cellular adhesion. A noticeable increase in lymphocyte adhesion to Kupffer cells previously treated with either trifluoroacetyl-guinea pig albumin or hepatocyte homogenate was observed. Stimulation of lymphocytes with phorbol myristate acetate did not have an effect on adhesion. Addition ofantimajor histocompatibility complex II antibody had a significant inhibitory effect on lymphocyte adhesion to Kupffer cells treated with trifluoroacetyl-guinea pig albumin or homogenate. CONCLUSIONS These results demonstrate that the halothane trifluoroacetyl-guinea pig albumin antigen and hepatocyte homogenate enhances the adhesion of lymphocytes to cultured Kupffer cells and that this interaction involves major histocompatibility complex II expression on stimulated Kupffer cells. The interaction between Kupffer cells which present specific trifluoroacetyl-antigens and lymphocytes from halothane-exposed animals may play an important role in the pathogenesis of halothane hepatitis.