A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115 (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was significantly correlated with HCV RNA according to the following equation: (log HCV RNA) ؍ 2.08 ؉ 1.03 (log HCV Ag) (R 2 ؍ 0.94; P < 0.001). As determined using a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter) as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%, and 99%, respectively. In conclusion, for a community study, HCV Ag showed good correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can provide the best result validity.C hronic hepatitis C virus (HCV) infection is a common etiology of liver cirrhosis and hepatocellular carcinoma, with an estimated 170 million chronic carriers worldwide (9, 22). Successful eradication of HCV has been shown to improve the prognosis of HCV-induced liver disease and reduce the associated mortality (23,27). Hence, to adequately screen individuals with an active infection is a crucial issue in areas where HCV is endemic (24).In clinical practice, diagnosis of HCV infection in hospitals is usually based on the detection of anti-HCV antibodies in the serum. Several anti-HCV assays have been used as the common serological marker for HCV infection for more than 20 years. However, most assays cannot distinguish infected individuals with an ongoing active infection from those who have recovered from acute infection. Unlike anti-HCV antibodies, serum HCV RNA is a reliable marker for the diagnosis of an ongoing HCV infection and is usually used for monitoring anti-HCV treatment. But its high cost, and the requirement for considerable technical skill and related equipment, limit its routine use in community screening (16).The HCV core antigen (HCV Ag) possibly exists in both complete HCV virions and RNA-free core protein structures and has been detected in the serum of infected individuals (8,13,20). Several HCV Ag assays developed in the last decade have been shown to have good correlation with HCV RNA assays (3,21,25,28). Hence, these assays were used as an alternative to HCV RNA for the diagnosis of active HCV infection as well as for the monitoring of the response...