Patients with chronic hepatitis C virus (HCV) infection (530 in toto), and 294 individuals with chronic liver disease of different aetiology, were enrolled in this study to investigate the prevalence of monoclonal gammopathies (MG) during chronic liver dysfunction. A monoclonal band was detected in 61 HCV+ patients and in nine HCV subjects only. In both instances, a correlation between MG presence and advanced age or degree of hepatic injury was noted. The prevalence of HCV genotype 2a was higher in HCV+ patients with, rather than in those without, MG. The MG+ HCV+ subjects did not exhibit human leukocyte antigen (HLA)-A33, B8, B65 and DR16 expression, while an increased frequency of DR15 structure was seen in the same group of individuals in comparison with MG- HCV+ patients and healthy donors. These findings suggest a possible relationship between HLA haplotype expression, virus genotypes and the occurrence of MG during the course of chronic HCV infection.