Serial assays for immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) were performed in 51 patients with antibody to hepatitis B e antigen (anti-HBe) in their sera. IgM anti-HBc was detected periodically and persistently in 8 (53%) of 15 patients with chronic hepatitis whose serum glutamic pyruvic transaminase (GPT) levels were elevated and was not detected in 36 patients with normal serum GPT levels. Antibody to delta agent was not detected in any of the patients. Of the eight patients positive for IgM anti-HBc, four had a high titer of IgM anti-HBc and either developed liver cirrhosis (three cases) or died due to massive hepatic necrosis (one case); the other four showed a low level of IgM anti-HBc and either recovered (two cases) or developed chronic persistent hepatitis (two cases). Of seven patients negative for IgM anti-Hbc, two had a fatty liver, and five, who had a history of blood transfusion, had chronic hepatitis. Thus, even though anti-HBe may be present, if the titer of IgM anti-HBc is high, the histological activity can be expected to increase, and the prognosis will be poor. If the titer of IgM anti-HBc is low, the histological activity may be expected to decrease, and the prognosis may be good. In patients with abnormally high serum GPT but without IgM anti-HBc, another type of hepatitis or a secondary form of liver disease should be considered.