We explored and studied cryoglobulins and autoantibodies in 149 patients with hepatitis C. 49% of untreated patients have cryoglobuliemia (36% polyclonal cryoglobulins) and 76% of ineffectively treated patients since more than 6 months (50% polyclonal cryoglobulins). Other observed cryoglobulins are half of type II and half oligoclonal. In 22 cryoglobulinemic patients before treatment, a good clinical response to IFN is induced only among patients for which cryoglobulins are negative at the end of treatment. Cryoglobulins could be indicators of viremia. The prevalence of autoantibodies is low and without clinical significance (they are more frequently detected in cryoglobulinemic patients, except anti-thyroid autoantibodies). Nevertheless, autoantibodies induced by IFN in our study (anti-thyroid autoantibodies, ANCA) are associated with clinical symptoms.