Hepatitis C virus (HCV) causes various extrahepatic immunologic abnormalities. Recently, an association between HCV infection and antiphospholipid syndrome, including thrombocytopenia, has been reported. However, the precise relationship between thrombocytopenia and anticardiolipin antibodies in patients with chronic HCV infection is not fully understood; likewise, the association of antiphospholipid syndrome and various liver diseases is not well understood. To evaluate the prevalence and importance of antiphospholipid antibodies in various chronic liver diseases, we determined the levels of anticardiolipin antibodies, platelet numbers, and levels of platelet-associated immunoglobulin G (PA-IgG) and thrombin-antithrombin III complex (TAT) in patients with chronic HCV infection, chronic hepatitis B virus (HBV) infection, and primary biliary cirrhosis (PBC). The prevalence of anticardiolipin antibodies in patients with HCV infection was significantly higher than that in control subjects or individuals with the other liver diseases examined. However, there was no significant correlation between anticardiolipin antibodies and platelet counts or TAT. The frequency of thrombotic complications was similar in anticardiolipin antibody-positive and -negative patients with chronic HCV infection. Further, sera from all but one anticardiolipin antibody-positive HCV patient were negative for phospholipid-dependent anti-beta2 glycoprotein I antibodies. Our results suggest that anticardiolipin antibodies are frequently found in patients with chronic HCV infection, but they do not appear to be of clinical importance. Immunologic disturbances induced by HCV or prolonged tissue damage in systemic organs as a result of the extrahepatic manifestations of HCV infection may induce the production of antibodies to various cardiolipin-binding proteins or phospholipids.