We assessed the correlation between hepatitis C virus replication and antibody responses toward hepatitis C virus core (C22-3), NS3 (C33C), NS4 (5-1-1 and C100-3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay. All 50 patients with high viremic levels of > or = 10(6) copies/mL had antibodies to C22-3 and C33C. Antibodies to 5-1-1, C100-3 and NS5 proteins were detected less frequently (p < 0.01) in 72% (36 of 50), 78% (39 of 50) and 84% (32 of 38) of such patients, respectively. As for the nine patients with low viremic levels of < 10(6) copies/mL, antibodies to C22-3, C33C, 5-1-1 and NS5 proteins were detected in only one patient (11%), which was significantly less than the frequency for highly viremic patients (p < 0.01). Antibody to C100-3 was also found less frequently in only four patients (44%) (p < 0.05). Thus, only four (44%) of the nine low viremic patients tested positive for any antibody compared with all 50 highly viremic patients (p < 0.01). These results indicate that highly viremic carriers can be detected by the presence of hepatitis C virus antibodies, but a considerable proportion of low viremic carriers may not show any serological evidence of hepatitis C virus infection.