Sera from persons infected with hepatitis B virus were fractionated into 19s and 7s moieties by high performance liquid chromatography and then tested for the antibody to hepatitis B core antigen (anti-HBc) of immunoglobulin M (IgM) class by radioimmunoassay. Sera from 17 patients with acute or fulminant hepatitis invariably showed a high activity of 19s IgM anti-HBc (sample/normal ratio 30.6 +/- 13.6). In addition, they all revealed a much lower activity of 7s IgM anti-HBc (4.1 +/- 3.4). In remarkable contrast, 7s IgM anti-HBc activity was higher than 19s IgM anti-HBc activity in the sera from 5 asymptomatic carriers (10.4 +/- 2.4 vs. 1.0 +/- 0.1), 4 patients with chronic persistent hepatitis (11.7 +/- 1.4 vs. 2.1 +/- 1.4), 13 with chronic active hepatitis (13.6 +/- 3.0 vs. 6.0 +/- 5.6), and 10 with liver cirrhosis (8.9 +/- 3.4 vs. 5.4 +/- 2.4). Among these 32 cases of persistent hepatitis B virus infection, there were only 2 (6.3%) in which the 7s IgM anti-HBc was lower than the 19s IgM anti-HBc. The proportion of patients who showed the value of 7s IgM anti-HBc exceeding that of 19s IgM anti-HBc was significantly higher for persistent (30 of 32) than for acute (0 of 17) hepatitis B virus infection (p less than 0.001). On the basis of these results, the determination of IgM anti-HBc in terms of 19s and 7s subpopulations would be useful for differentiating acute from chronic hepatitis B virus infection, especially when the titer of IgM anti-HBc is not high enough to exclude a persistent hepatitis B virus infection.