Eicosapentaenoic acid (EPA) has been shown to exert anti-inflammatory actions. To evaluate the effects of EPA on chronic hepatitis C, we administered EPA ethyl ester capsules to patients receiving the combination therapy of interferon alpha-2b and ribavirin. EPA (1,800 mg/d) was supplemented in combination with vitamin E (300 mg/d) and C (600 mg/d) to 5 chronic hepatitis C patients (EPA group). Five patients were administered vitamin E and C but not EPA (control group). Blood samples were obtained before and after 4, 8, 12 and 24 wk of therapy and analyzed for fatty acid compositions of erythrocyte and plasma and serum 8-hydroxy-2'-deoxyguanosine. EPA in erythrocyte membrane rose to 3 fold the basal level in the EPA group, while it decreased significantly in the control group after 24 wk of therapy. Lymphocyte counts in the EPA group increased to 120.8 +/- 25.4% after 4 wk of therapy and maintained the basal level throughout therapy, whereas the counts decreased significantly in controls. The serum alanine aminotransferase level was improved significantly in the EPA group. Changes in lymphocyte counts following 24 wk of therapy correlated with the EPA level in erythrocyte. The serum 8-hydroxy-2'-deoxyguanosine level at 24 wk in the EPA group was significantly lower than that in controls. These observations may suggest the beneficial effect of EPA supplementation in the treatment of chronic hepatitis C patients.