Apoptosis is a type of cell death that occurs in acute or chronic hepatitis. It has been suggested to be mediated through Fas antigen. To evaluate the role of apoptosis on liver injury of chronic hepatitis C, we studied the expressions of Fas antigen and hepatitis C virus antigen (core antigen) immunohistochemically. Forty liver biopsy samples from patients with type C chronic liver disease were immunostained for Fas antigen and hepatitis C virus antigen. Expression of Fas antigen was found mainly in the cytoplasm of hepatocytes, and these positive cells were found particularly among infiltrating lymphocytes at the advancing edges of "piecemeal necrosis." The histological activity index showed inflammation of both portal and periportal areas to be more severe in the Fas antigen-positive samples than in the Fas antigen-negative ones (p < 0.05 and p < 0.001, respectively). Furthermore, semiquantitative analysis revealed more expression of Fas antigen in the liver tissues with active inflammation than in those without it (p < 0.01). The prevalence of Fas antigen expression in the hepatitis C virus antigen-positive group was higher than that in the hepatitis C virus antigen-negative group (p < 0.05). Our findings suggest that Fas antigen expression (apoptosis) plays an important role in inflammation in the hepatitis C virus-infected liver, particularly in the active inflammation of chronic hepatitis C.