Patients with hereditary bleeding disorders who received non-virally inactivated plasma-derived clotting factor concentrates before the mid-1980s invariably became infected with hepatitis C virus (HCV). Therapy with interferon alpha (IFN-α) alone has been disappointing in this group. We conducted an open-label study, using a combination of IFN-α2b (3 million units three times per week) and ribavirin 1–1.2 g/d in 28 patients with hereditary bleeding disorders. Twenty-one of the 28 patients had liver biopsy-confirmed chronic hepatitis (median histological activity index 5; range 1–10) and all patients were HCV RNA positive by PCR. Virological response rate to therapy at 3 months was 82% (23 out of 28). Three HIV co-infected patients showed an early virological response with loss of HCV RNA, but two subsequently relapsed after 3 and 6 months of therapy. Four patients stopped treatment early (one at 4, one at 7 and two at 9 months) because of treatment-related side effects, although three of these have maintained a virological response. Seventeen patients completed the 48-week course. Twenty of the 28 (71%) treated have had a durable virological response with a median follow-up of 16 months (range 1–24). Combination therapy represents a significant advance in the treatment of hepatitis C in patients with hereditary bleeding disorders.