The prevalence of hepatitis C virus (HCV) RNA and of antibodies to HCV in an unselected series of 42 mixed cryoglobulinemia patients was investigated in this study. HCV RNA was detected by the polymerase chain reaction technique, and HCV antibodies by two enzyme-linked immunosorbent assays (Chiron ELISA HCV, Second Generation, Emeryville CA, USA; Wellcome Diagnostic, England). HCV RNA was found in 86% of the mixed cryoglobulinemia patients. Using either the Chiron ELISA or the Wellcome ELISA, HCV antibodies were present in 90% of the same samples; anti-HCVAb seropositivity was confirmed in all cases by immunoblot assay (Chiron RIBA HCV, Second Generation Assay). A striking correlation between HCV RNA and anti-HCV antibody seropositivities was recorded. HCV RNA in mixed cryoglobulinemia patients was not correlated with the presence or absence of biopsy-proven liver involvement. These results suggest that the association between HCV and mixed cryoglobulinemia is not fortuitous, and therefore that HCV may have an etiopathogenetic role in this disorder.