Occult HCV infection has been described among anti-HCV-HCV RNA-negative individuals with abnormal transaminase values in whom HCV RNA is detected in liver.IgG antibody to an HCVcore-derived peptide (anti-HCVcore) was investigated in 145 patients with serologically silent occult HCV infection.At the time of the diagnostic biopsy 45/145 (31%) occult HCV-infected patients tested IgG anti-HCVcore-positive but none of the 140 patients with HCV-unrelated liver disease (P<0.001). Among 23 IgG anti-HCVcore-positive patients at baseline, 22 remained antibody-reactive (one became antibody-negative). Similarly, 17/31 baseline anti-HCVcore-negative patients remained non-reactive whereas 14 seroconverted to IgG anti-HCVcore (although transiently in 10 patients). Thus, a total of 59/145 (40.7%) patients with occult HCV infection showed IgG anti-HCVcore reactivity at any time point analyzed, including 14 initially non-reactive patients. By supplemental immunoblot assay 16 sera reacted weakly with an HCVcore-peptide band (indeterminate result) of which 10 (62.5%) reacted in the IgG anti-HCVcore assay. Occult HCV-infected patients who tested anti-HCVcore-positive showed more frequently signs of necro-inflammation (P=0.035) and greater percentages of HCV RNA-positive hepatocytes (P=0.004) compared with those anti-HCVcore-negative.This work documents that IgG anti-HCVcore testing identifies occult HCV infection among seronegative, non-viremic patients using screening tests and may be useful in tracking anti-HCV-negative infections.