- We evaluated the significance of IgA antibodies directed against the hepatitis B virus core antigen (IgA anti-HBc) as a marker for viral replication. Serum samples of 143 hepatitis B surface antigen (HBsAg) carriers and 189 HBsAg-negative subjects were studied. Hepatitis B virus (HBV) DNA was detected by polymerase chain reaction. IgA anti-HBc was determined by a capture enzyme-linked immunosorbent assay developed in our laboratory. The results were compared with those for IgM anti-HBc, which were determined by a commercially available method. IgA anti-HBc was detected in 57 (40%) and HBV DNA in 38 (27%) of the HBsAg carriers. Among the HBsAg-negative subjects, IgA anti-HBc and HBV DNA were detected simultaneously in four samples. All 42 HBV DNA-positive samples were IgA anti-HBc positive. IgM anti-HBc was detected in 27 (64%) of them. IgA anti-HBc is a sensitive marker for HBV replication, and its absence may exclude HBV replication. The role of IgA anti-HBc in monitoring response to therapy and predicting clinical course is being evaluated.