In patients with chronic hepatitis C, prior studies have suggested that increased hepatic iron concentration (HIC) is predictive of a poor response to interferon (IFN) monotherapy. The aim of this study was to assess the importance of HIC on the virologic response to therapy with IFN alone or when combined with ribavirin. Records of 91 patients were reviewed for inclusion in this study. Fifty-one received IFN alone, and 40 received IFN plus ribavirin. HIC and serum iron studies, alanine aminotransferase (ALT) values, hepatitis C virus (HCV) genotype, and HCV RNA were determined prior to therapy. Sustained response was defined as the absence of HCV RNA 6 months after the end of therapy. In the IFN monotherapy group, mean HIC was higher for nonresponders (803 + 89 microg/g, range 130-2808 microg/g) compared with sustained responders (241 + 54 micro g/g, range 187-295 microg/g) (p < 0.01). In contrast, in the combination therapy group, the mean HIC was similar for both groups (533 + 86 microg/g, range 79-1338 microg/g in the nonresponders, and 662 + 95 microg/g, range 94-2031 microg/g, in the sustained responders). No difference between transferrin saturation and serum ferritin level was observed in sustained responder or nonresponder patients treated with IFN plus ribavirin. IFN monotherapy nonresponder patients tended to have a higher HIC. With IFN plus ribavirin, the sustained virologic response rate was not affected by the HIC.