To assess the role of anti-c100 antibodies to hepatitis C virus (anti-c100 HCV) in the response to interferon (IFN) administered to patients for the treatment of chronic hepatitis C, we assayed serum anti-c100 HCV serially by means of an enzyme-linked immunosorbent assay (ELISA) kit and titrated anti-c100 HCV level by a radioimmunoassay (RIA) kit in 28 IFN-treated and 20 untreated patients with chronic hepatitis C. IFN-alpha or -beta was administered for 4 to 12 weeks, and the patients were observed for over 24 months. The IFN-treated patients were divided into 3 groups (4 sustained responders, 18 transient responders, and 6 non-responders) in accordance with their responses on the basis of the serum alanine aminotransferase levels. In three of the four sustained responders whose HCV-RNA decreased, anti-c100 HCV became negative at 13, 15, and 17 months after beginning the IFN therapy. The 18 transient responders and 6 non-responders remained positive for anti-c100 HCV throughout the observation period. In all four sustained responders the anti-c100 HCV titer decreased significantly with time after initiation of the therapy, whereas the titer fluctuated in the other groups. These findings suggest that monitoring the serum anti-c100 HCV level is useful in assessing the effects of IFN therapy on chronic hepatitis C.