AbstractBecause of widely differing reports on the significance of IgM anti‐HBc in chronic hepatitis B virus (HBV) infection, paired sera and liver biopsies from 49 patients with chronic HBV infection were analysed for serum IgM anti‐HBc, HBsAg titre, HBeAgianti‐HBe, HBV DNA, serum aspartate transaminase, intrahepatic HBcAg expression, and liver histology. High levels of IgM anti‐HBc, i n the diagnostic range of acute hepatitis B (>1.2), were detected in seven patients (14.3%) and a total of 34 patients (69.6%) had an index of more than 0.2. No correlation was found between IgM anti‐HBc and the serum markers of active viral replication or HBsAg titre but it correlated significantly with intrahepatic expression of cytoplasmic HBcAg (r2= 0.165,P=0.002). IgM anti‐HBc also correlated with active liver histology (P= 0.015) but there was a considerable overlap of the IgM anti‐HBc index values between the various disease groups, indicating a poor specificity. Serial assessment of IgM anti‐HBc in eight patients treated with interferon‐α (four responders) showed an increase in IgM anti‐HBc in three out of four patients corresponding to the e‐seroconversion period followed by a drop in IgM anti‐HBc levels. However, an increase in IgM anti‐HBc was also seen in one non‐responder, indicating that this feature is not unique to interferon‐α responders. These data indicate that serum IgM anti‐HBc cannot be used alone as a certain diagnostic measure of HBV replication nor in