Interferon (IFN) therapy of chronic hepatitis C has proved useful in recent years. A major goal in the treatment of hepatitis C is the prevention of the high relapse rate after cessation of therapy and the improvement of the response rate in non-responders. Several approaches can be tried. The administration of higher doses of IFN results in an increase in the response rate, but does not prevent ultimate relapse. Similarly, prolongation of the treatment period gives better results, but one third of cases still relapse. In these cases, re-treatment results in ALT normalization once again, but does not prevent subsequent relapse; in non-responders to IFN, re-treatment will not lead to improvement of the response rate. Analysis of the viral genome reveals its presence in serum in spite of the normalization of ALT values. The role of HCV genome heterogeneity in the response to IFN needs to be assessed and it is necessary to find other antiviral agents that are able to clear HCV from all relevant hosts (serum, liver tissue and mononuclear cells).