Infection of a hepatitis C virus (HCV) is confirmed by the presence of HCV antibody or HCV-RNA. Recently, a highly sensitive method to examine HCV-core antigen has been developed. In this study, to evaluate the clinical significance of HCV-core antigen determination, we examined serum HCV infection markers, HCV-core antigen, HCV-RNA (AMPLICOR) and HCV-antibody (third generation) concentrations. We determined 225 serum samples, and three patients receiving the treatment with interferon. In 102 HCV-RNA positive samples, significant correlation was observed between HCV-RNA and HCV-core antigen (r=0.734, p<0.0001). However, three out of 102 (2.9%) cases were included within the negative range of HCV-core antigen (20 fmol/l). The HCV-core antigen value in three patients receiving the treatment with interferon paralleled with the amount of HCV-RNA. The determination of HCV-core antigen by CLEIA is a useful and time-saving method, but an attention should be paid to the presence of false-negative cases.