Hepatitis C virus (HCV) infection frequently causes chronic hepatitis and lack of virus clearance in these patients. In addition, many patients infected by HCV also present with hypergammaglobulinemia in the early stage of chronic infection. These observations raise a possible viral superantigen effect induced by HCV, because viral superantigen found in human immunodeficiency virus (HIV) or in replication of defective murine leukemia virus (MuLV) is associated with T-cell dysfunction and polyclonal activation of B cells. The possibility was investigated of whether HCV encodes any superantigen by analyzing the usage of T-cell receptor (TCR) from the peripheral blood lymphocytes (PBL) of patients with chronic hepatitis C. Two groups, one with hypergammaglobulinemia and the other without hypergammaglobulinemia, were studied for the usage of TCR beta chain by reverse transcription-polymerase chain reaction (RT-PCR) analysis. It was found that all genes of V beta variable chain were used in the PBL of these patients. Furthermore, there was no significant difference of the TCR expression pattern between these two groups, nor a complete deletion of a particular T-cell subset in either group. These results do not provide evidence for HCV superantigen, but indicate that the TCR usage in the patients was neither defective nor biased.