In a long-term study (27 months) of patients affected by C-virus active hepatitis we have evaluated the effect of decreasing the dose of interferon by 50% and by 75% with respect to the initial efficacious dose (6 MU tiw). Sixty patients received recombinant interferon alpha-2b(r-IFN- alpha-2b) 6 MU tiw for two months followed by 3 MU for seven months (Group A), and 60 patients received r-IFN alpha-2b 6 MU tiw for two months followed by 1.5 MU for seven months (Group B). Three patients in group B failed to return to follow-up and were not considered in subsequent evaluations. Side effects such as to cause suspension of treatment occurred only during the first two months of the study at 6 MU of interferon (3 patients in group A and 6 in group B). During the two months at 6 MU, transaminase values returned to normal in 94 patients (80%). At the end of follow-up, 49 of these patients (42% of the 117 patients examined; or 48.3% in group A and 35.1% in group B) had normal transaminase levels. In no case did the anti-HCV test become negative. On a reduced dose of interferon, relapses occurred more frequently in group B (21.4%) than in group A (9.6%), but the difference was not significant. No difference between responders and non-responders, including relapsing patients, was observed in relation to gender, age, presence of cirrhosis, presence of B-virus antibodies and initial levels of serum transaminase.