The aim of this study was to investigate whether there is a variable responsiveness of the hepatitis C virus and/or of the affected host to different types of interferon. We treated 21 patients affected by chronic hepatitis C who failed to respond to recombinant alpha interferon, after a four-month interval, with lymphoblastoid interferon. Alanine transaminase (ALT) serum level was normal in 9 patients (43%) at the end of treatment. At the end of a 12 months treatment-free follow-up serum ALT remained normal in 3 patients, 4 patients relapsed and 2 dropped-out. As yet there are no reports of differences in the therapeutic efficacy of the two types of interferon used in our study. The good response to the lymphoblastoid interferon in our non responders to recombinant alpha interferon may be due to the immune modulation induced by the four-month wash-out interval between the two therapies or to a different virus sensitivity to this interferon.