Cryoglobulins are immunoglobulins that precipitate at low temperatures. They are easy to characterize by using sensitive techniques such as immunofixation and immunoblotting. Recently, hepatitis C virus (HCV) has been found to be associated with essential mixed cryoglobulinemia. The different frequencies reported might be explained by heterogeneity in patient subpopulations and advances in serologic rests. In addition to commercial kits detect HCV antibodies, polymerase chain reaction (PCR) of HCV RNA can now be applied to serum or cryoprecipitates. The pathogenic role of hepatitis C virus is well-known, but the precise mechanism remains to be determined.