Serum samples from 130 persons who were seropositive for hepatitis B surface antigen and who had various forms of accompanying liver disease were tested for immunoglobulin M (IgM) antibody to hepatitis B core antigen. In 99% of patients with hepatitis B antigen-positive chronic type B hepatitis, IgM antibody to hepatitis B core antigen was present. This antibody was not present in "healthy" hepatitis B surface antigen carriers and was detectable in only 30% of patients with delta hepatitis. Testing of serial sera from 38 patients with chronic type B hepatitis revealed that IgM antibody to hepatitis B core antigen persisted in patients who had evidence of persistent hepatitis B virus replication but ultimately disappeared in those patients who exhibited a sustained loss of serum markers of viral replication (hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity). These findings suggest that the presence of IgM antibody to hepatitis B core antigen in chronic hepatitis B surface antigen carriers indicates an active immune response to persistent viral replication.