Type II cryoglobulinemia may be associated with chronic hepatitis C virus (HCV) infection and may be characterized by vascular purpura. We report on a case of histologically proven necrotizing vasculitis associated with type II cryoglobulinemia and HCV infection. Within 14 days of interferon-alpha therapy (3 x 3 million IU/ml/week), purpuric skin lesions disappeared as well as fatigue and arthralgia; 9 months after initiation of therapy, liver enzyme values were nearly normal despite persistence of HCV RNA tested by PCR and mixed cryoglobulinemia. Rheumatoid factor activity, however, decreased markedly. To our knowledge, our patient is the first reported case with histologically proven necrotizing vasculitis with a beneficial effect of interferon-alpha. Because of the persistence of cryoglobulins, but reduction of the IgM fraction in the cryoglobulin complex under interferon-alpha treatment, it would seem worthwhile to further elucidate the pathogenic role of qualitative instead of quantitative changes of cryoglobulins and the mechanism of action of interferon-alpha.