We investigated the clinical usefulness of a new immunoradiometric (IRM) assay of hepatitis C virus (HCV) core antigen in predicting virological response during pegylated interferon plus ribavirin (PEG-IFN/RBV) combination therapy for chronic hepatitis with high viral loads of serum HCV RNA genotype 1b. Thirty-nine patients received a regimen of PEG-IFNalpha-2b (1.5 microg/kg/week s.c.) in combination with RBV (600-1,000 mg/day). Of the 39 patients, 18 (46.2%) achieved sustained virological response (SVR), 11 (28.2%) attained partial response (PR) and 10 (25.6%) showed no response (NR). Four weeks after the start of therapy, 1- and 2-log reductions in the amount of HCV core antigen were observed in 20 (2/10) and 0% (0/10) showing NR, 91 (10/11) and 63.6% (7/11) with PRs, and 88.9 (16/18) and 55.6% (10/18) of patients with SVR, respectively. The 1- and 2-log reductions 4 weeks after the start of therapy were not a defining condition for PR and SVR. The amount of HCV core antigen was significantly different between SVR and PR patients on days 1 and 7, and between patients with NR and SVR at all points of time. In conclusion, this new IRM assay is useful in predicting virological response during PEG-IFN/RBV therapy. Copyright 2008 S. Karger AG, Basel.