In order to assess the efficacy of interferon-alpha on hepatitis C viral RNA in patients with chronic hepatitis C, we analyzed the levels of HCV RNA in sera and liver tissues of 16 patients pre- and posttreatment using a semiquantitative polymerase chain reaction method. Fifteen of 16 patients were positive for anti-HCV antibodies by four-antigen recombinant immunoblot assay (4-RIBA). Only two patients demonstrated normalization of ALT in response to interferon; three patients showed a partial response. Only one patient from the partial responder group displayed a significant reduction of HCV RNA level posttreatment. In the nonresponder group, several patients, although their ALTs remained elevated, demonstrated significant decreases in HCV RNA levels in either serum or liver in response to interferon. Our data suggest that interferon treatment of chronic hepatitis C may not be effective in eradicating HCV infection and a reduction in ALT is infrequently associated with a decrease in HCV RNA level in either serum or liver. Cessation of treatment is frequently associated with the recrudescence of HCV replication and disease.