Increased prevalence of HCV infection in some lymphoproliferative diseases has been recently reported. In the present study, the frequency of anti-HCV antibody (Ab) together with hepatitis B surface (HBs) antigen (Ag) and anti-HBs Ab were determined in 42, 45 and 23 patients with essential mixed cryoglobulinemia (EMC), multiple myeloma (MM) and B-cell chronic lymphocytic leukemia (B-CLL), respectively. Thirty hospitalized patients with chronic rheumatoid arthritis (RA) were also included as a control. Specific antibodies to HCV antigens were detected by enzyme linked immunosorbent assay (ELISA) and positive results were confirmed by a recombinant immunoblot assay (RIBA). Our results demonstrated anti-HCV positivity in 69%, 11% and 4.3% of the EMC, MM and B-CLL samples tested, respectively. None of the RA patients were found to be anti-HCV positive. No significant differences were observed between the patients groups regarding the frequency of HBs Ag and anti-HBs Ab. Considering the low incidence of HCV infection in the control group and the normal population, these results confirm and extend previous reports on the possible role of HCV infection in the etiology of EMC and further suggest involvement of this virus in a subset of MM.