Determination of time sequence of pre-S2 and its antibody response during the symptomatic phase of acute viral hepatitis type B, as well as their relationship to the HBV-markers, was carried out in 30 subjects after the onset of liver damage by means of monoclone antibody-captured enzyme immunoassay were analysed. The results showed that anti-pre-S2 were positive in 80.3% of patients recovering from acute viral hepatitis type B, being higher than the percentage during maximal liver damage (P less than 0.001). Such antibodies were absent in cases showing chronic evolution and were found in less than 8% of chronic hepatitis B cases, with no relation to liver damage. Anti-pre-S2 were detected after the immune clearance of HBsAg and HBV-DNA, and thereafter the anti-HBs were present in 80% of patients after recovery (P less than 0.001). Our observations significantly suggest that anti-pre-S2 may be valuable as a marker of the favourable prognosis of acute viral hepatitis type B and of HBV clearance. They did not play any role in the pathogenesis of HBV-related liver damage. The continuous presence of pre-S2 with the absence of anti-pre-S2, on the contrary, is considered as a characteristic sign and a new information of chronic viral hepatitis type B.