Antibodies to hepatitis B core antigen (anti-HBc) and e antigen (anti-HBe) were assayed in 46 sera from ten patients with acute hepatitis B utilizing immunoglobulin class-and subclass-specific enzyme immunoassays (EIAs). The sera were sampled 1 to 512 days after onset of hepatic symptoms. Four patients cleared HBsAg rapidly, within 24 days, and six patients cleared HBsAg slowly, within 27-74 days after the onset of symptoms. In three of the patients with rapid clearance of HBsAg, hepatitis B virus (HBV) DNA was not detected in sera tested during the first week after onset. The fourth patient was not tested until 12 days after onset and was then found to be negative for HBV DNA. In four of the patients with slow clearance of HBsAg, HBV DNA was present during the first week of illness. In the other two patients, HBV DNA was not detected in the first serum, 11 and 17 days after the onset of illness. Anti-HBc IgM and l g A l were detected in all patients, with maximum titers shortly after onset. Anti-HBc lgGl was present in all sera tested. Anti-HBc lgG2 was not detected in any of the sera. Anti-HBc lgG3 and lgG4 were detected in all patient sera, with lgG3 paralleling IgG1, and lgG4 mainly in sera long after onset. Anti-HBe IgG1, lgG3, and lgG4 were detected in three, two, and t w o patients, respectively. Anti-HBe lgG2, IgM, IgAl, or lgA2 was not found in any patient. The time required for maximum titer of anti-HBc lgGl was shorter in the patients with rapid clearance of HBsAg. Thus, in these patients, the geometric mean titer (GMT) of anti-HBc lgGl had not increased significantly, in sera sampled 56-182 days after onset, whereas, in the patients with slow clearance of HBsAg, the increase in GMT of anti-HBc lgGl was significant ( P < 0.05; Student's t test). The humoral responses to HBcAg and HBeAg in acute hepatitis B differ in that HBcAg elicits a vigorous IgM or l g A l response whereas HBeAg elicits only low levels of IgG, mainly IgG1. Thus our findings support differences regarding T-cell depen-\o 1989 ALAN R. LISS, INC. dence, when comparing the humoral responses to HBcAg and HBeAg.