For chronic hepatitis C virus (HCV) infection, interferon-alpha (IFN-alpha) treatment has recently been established. However, the complete responding rate is not higher than 20-25%. The aim of our study was to assess IFN-alpha retreatment in chronic hepatitis C. In summary, during a second cycle of IFN-alpha, 60% of the patients responded to the retreatment. Indeed, a sustained complete response, together with long-lasting normal alanine aminotransferase values and negative serum HCV-RNA, was observed in about 40% of the retreated patients. Future prospective and controlled trials must define the optimal retreatment strategy, as well as the response-predicting factors including HCV genotypes and quantitative HCV-RNA levels.