Objective. Mixed cryoglobulinaemia is closely associated with hepatitis C virus (HCV) infection. The aim of this trial was to evaluate in a prospective open study the efficacy of ?-interferon in the treatment of chronic hepatitis C virus associated to mixed cryoglobulinaemia (MC). Methods. Thirty-one consecutive patients were treated for the first time with ?-interferon at a dose of 6 MU three times a week for 12 months. All the patients presented cryoglobulins, which were responsible for clinical manifestations in 9. Results.At the end of interferon treatment, 11 patients presented complete responses (biochemical and virological), including 7 subjects who presented MC-related clinical manifestations. Cryoglobulins had disappeared in 48.4% of the patients and a clinical improvement was observed in 7 out of 9 patients. Twelve months after interferon treatment was stopped, only 25.8% of patients still had undetectable cryoglobulins and 5 subjects who presented complete responses, all with MCrelated clinical manifestations had a relapse both of HCV-related biochemical and virological indexes and of MC clinical manifestations. Conclusions. A 12-month course of ?-interferon is effective treatment for HCV-related cryoglobulinaemia, especially during therapy. However we obtained scarce results in the follow-up above all in the patients with clinical manifestations of MC.