Antibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay in 127 asymptomatic hepatitis B surface antigen (HBsAg) carriers (ASC; mean age 19) who had normal serum alanine aminotransferase (ALT) levels and 16 patients with chronic hepatitis B (CH; 19). All 16 CH patients, who were positive for hepatitis B e antigen (HBeAg) and 5 ASC cases who were negative for both HBeAg and its antibody (anti-HBe), had high anti-HBc titers. Anti-HBc titers in 27 (56.3%) of the 48 HBeAg-positive ASC and 18 (24.3%) of the 74 anti-HBe-positive ASC were relatively low. Two of the ASC were HBeAg-positive/anti-HBc-negative. In a follow-up study of the 19 HBeAg-positive ASC with low or negative anti-HBc titers, 5 had abnormal serum ALT levels and increased anti-HBc titers. In contrast, in the other 14 of these subjects, serum ALT levels remained normal and the low anti-HBc titers remained unchanged and/or decreased. The serological profile of HBsAg-positive/low or negative anti-HBc titer and increased anti-HBc titer with abnormal serum ALT levels are not necessarily exceptional in HBeAg-positive adolescent ASC. It is suggested that anti-HBc is associated with the liver damage that occurs before adolescence in chronic hepatitis B virus infection.