Polypeptides encoded by the pre-S1 and pre-S2 genes of hepatitis B virus (HBV) (pre-S1 antigen and pre-S2 antigen) were detected by enzyme-linked immunosorbent assay (ELISA) in 137 serum samples of patients with HBV infection. The HBV-DNA level closely correlated with the titer of pre-S antigens. However, HBV-DNA levels more closely correlated with the titer of the pre-S1 antigen [HBV-asymptomatic carrier (ASC): n = 40, r = 0.800, P less than 0.01; chronic hepatitis B (CH): n = 60, r = 0.730, P less than 0.01] than with the titer of the pre-S2 antigen [ASC: r = 0.675, P less than 0.01; CH: r = 0.575, P less than 0.01]. Thirty patients with CH, in whom hepatitis e antigen (HBeAg) was cleared after acute exacerbation (AE) [alanine aminotransferase (ALT) level greater than 200 IU/L] and the ALT level normalized, were followed for 12 months and classified into two groups: Group 1, those in whom HBeAg reappeared with an elevated ALT level within 12 months, and Group 2, those in whom HBeAg was persistently cleared from the serum and a normal ALT level continued. Of the 30 patients, 24 (80%) were classified into Group 1 and 6 (20%) were classified into Group 2. Changes in serum levels of HBV markers a month before and after AE were observed. The HBV-DNA level and DNA-P activity became negative after AE in both groups. The titer of pre-S1 antigen also decreased after AE, and no significant differences were observed between Group 1 and Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)