Twenty-four patients with chronic active HCV infection, nonresponders to a previous treatment cycle with recombinant interferon-alpha (r-IFNA), underwent retreatment with leukocyte (LE-) IFN-alpha. This was administered at the dose of 3 MU three times a week, for either six months (group A) or 12 months (group B). All patients were followed-up for a further 12 months. ALT levels significantly (P < 0.05) decreased in group A, with complete response in three cases and a partial response in a further three at the end of treatment. During follow-up all patients again showed increases in ALT values. In group B also ALT significantly (P < 0.05) decreased, with two complete and five partial responses. During follow-up, apart from two patients with partial responses who relapsed, all maintained their initial response. At the end of treatment HCV RNA was no longer detectable in complete responders of both groups, while it was found reduced in those partial responders who maintained their response during follow-up. Partially responding subjects treated for six months evidenced higher levels than those treated for 12 months. IFN-alpha retreatment could therefore be effective in previously nonresponding patients, with a change in the type of interferon administered and the use of higher dosages and/or longer treatment periods.