We have retrospectively analyzed a series of 19 patients with hepatitis C virus (HCV) infection and chronic thrombocytopenia not attributable to hypersplenism or to other causes. Antiplatelet antibodies were present in 81% of cases. Response to prednisone was observed in 6 of 7 patients and 1 of 3 patients responded to intravenous immunoglobulins. No case of reactivation of liver disease was observed during or after therapy. We consider that the possibility of an underlying mechanism should be evaluated in thrombocytopenic patients with HCV infection who do not present hypersplenism. These patients could benefit from steroid treatment.