Background and Objectives: Despite improvements in assays for anti-HCV, there remains a significant delay before the appearance of antibodies following infection, during which, circulating viral RNA is present. We have evaluated a prototype assay for the serological detection of hepatitis C virus (HCV) core antigen with specimens derived from the early phase of HCV infection. Materials and Methods: Serial specimens from 24 individuals undergoing HCV seroconversion were tested for the presence of anti-HCV, HCV RNA and HCV core antigen. Results: HCV antigen was detected at the same time as HCV RNA in 83% (20/24) cases. The mean time to the first detection of HCV antigen was approximately 1 day later than HCV RNA. Overall, 87% of HCV-RNA-positive specimens contained detectable HCV core antigen. Conclusion: These results indicate that HCV core antigen can be identified by routine serological ELISA in specimens from the early antibody-negative phase of HCV infection. A test for HCV core antigen may be a useful test for identifying window phase blood donations from antibody negative donors infected with HCV. Copyright (C) 2000 S. Karger AG, Basel.