Response to interferon therapy in chronic hepatitis B virus (HBV) carriers is preceded by the appearance of IgM class anti-HBc (antibody to hepatitis B core antigen). The temporal relationship and magnitude of the IgM anti-HBc response is variable suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins, induced by interferon. IgG 1, 2, 3, and 4 class anti-HBc did not change during therapy, but IgG 3 anti-HBc was significantly lower in responders than non-responders. IgG anti-HBc of all subclasses was absent in two Chinese HBV carriers. Lower than normal titres of anti-HBc (p less than 0.001) were detected in human immunodeficiency virus antibody positive (anti-HIV) HBV carriers. These data indicate the presence of altered immunity to the nucleocapsid antigens in these two types of chronic HBV carrier that are known to respond poorly to antiviral therapy.