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The specific etiologies of the cryoglobulins in HCV infection are unknown but may relate to two specific immunologic features of HCV: the virus evades immune elimination in most patients and in some patients it induces monoclonal rheumatoid factors (RF). As a result of these features there is chronic infection associated with chronic formation of an immune complex containing polyclonal, oligoclonal and monoclonal immunoglobulins. Some immune complexes precipitate in the cold in vitro, i.e., cryoglobulins. Only some immune complexes are associated with disease. The clinical syndrome of mixed cryoglobulinemia (Meltzer-Franklin syndrome) is a systemic vasculitis that affects mainly skin, kidneys, and nerves. In type II, the cryoglobulins consist of polyclonal IgG and monoclonal IgM RF; in type III, both the IgG and IgM RF are polyclonal. Approximately 90 % patients with the mixed cryoglobulinemia syndrome are HCV infected. A highly restricted monoclonal RF that bears an antibody-combining site epitope called the WA cross-idiotype is present in approximately 80 % of patients with symptomatic type II cryoglobulinemia. HCV along with VLDL appear to be selectively concentrated with type II cryoglobulins in vitro. Clinical manifestations occur predominantly with type II cryoglobulins. There appears to be a variable pathogenic role of HCV in mixed cryoglobulinemia. The palpable purpura (leukocytoclastic vasculitis) lesions of the skin appear to be due to complexes of HCV, mRF and RF formed in situ. In contrast, HCV has not been detected in the glomerular deposits in the membrano-proliferative glomerulonepritis (MPGN) or in the vascular deposits in the peripheral nerve lesions. Reports o