We present 10 cases of mixed cryoglobulinemia in patients infected with hepatitis C, including pertinent clinical, serologic, and pathological data. The findings attributable to MC appear to be similar in patients who are HCV-infected as in those with unknown HCV status. The prevalence of MC in HCV-infected patients appears to be lower in our region (13%) than in southern Europe (50-90%) although some of this difference is due to our requirement that patients included in our study have a cryocrit of at least 5%. In our patients, cryoglobulins were shown to be deposited in skin and kidney, but not in liver. The mechanisms by which HCV and MC are related remain uncertain. Although we and others have evidence for enrichment of HCV RNA in the cryoprecipitates of some patients, this was not always the case, and it is not yet clear that this finding is of fundamental pathogenic importance. Finally, it appears that some patients with HCV and MC may have a beneficial clinical response of vasculitic symptoms to therapy with alpha-interferon, as well as to glucocorticoids or other immunosuppressants. In our group, no predictors were apparent to distinguish responders from nonresponders before treatment. Similarly, the duration of response remains to be determined.