Bile duct damage in patients with chronic hepatitis C (hepatitis-associated bile duct lesion) as well as that in patients with primary biliary cirrhosis (PBC; chronic non-suppurative destructive cholangitis), may be causally related to immunological assaults. Efficient antigen presentation is known to require the provision of a costimulatory signal which is dependent on the CD28 on T cell surfaces, and that at least two molecules, B7-1 and B7-2, work as costimulatory ligands for CD28. In this study, we examined immunohistochemically, the expression of B7-2 in portal tracts of liver biopsy specimens obtained from 75 patients with chronic hepatitis C who had hepatitis-associated bile duct lesions, and from 63 PBC patients with chronic non-suppurative destructive cholangitis. B7-2 positive cells were recognizable as large mononuclear cells scattered in portal tracts. Some of these cells showed a dendritic cell-like appearance. B7-2 positive cells were observed more frequently (41%) in PBC liver specimens than in chronic hepatitis C specimens (17%, P < 0.05). In PBC livers, such cells were preferentially observed around the damaged bile duct with a few located in the biliary epithelial layer. There was no such finding in chronic hepatitis C livers. The frequency and density of B7-2 positive cells in the liver specimens tended to decrease according to the stage of PBC (45% in stages 1 and 2, and 33% in stages 3 and 4; P = 0.10), whereas with chronic hepatitis C, no such tendency was observed. These findings suggest that B7-2 positive cells may play a role in the bile duct lesions that appear in the early histological stages of PBC and that the immunological mechanisms of bile duct damage, particularly of antigen presentation and B7-2 expression, differ between PBC and chronic hepatitis C.