Objective To investigate the effects of "a determinant variants in chronic hepatitis B(CHB)patients on the expression of hepatitis B surface antigen(HBsAg) and anti-HBs antibodies (HBsAb). Methods Eight hundred sixty-six chronic hepatitis B patients were enrolled, which HBs Ag carriage was beyond a 6 month period.77 patients(8.9%)concomitantly carried both HBs Ag and anti-HBs antibodies,789 patients(91.1%)were only HBs Ag positive. Selection criteria for patients with both HBs Ag and anti-HBs were mainly focused on anti-HBs titers at least three times above the analytical threshold of the technique(10 U/L)on at least three consecutive visits.14 patients were selected from77 patients, who presented both markers(group Ⅰ),and 12 patients from another 789 patients who positive for HBs Ag only(group Ⅱ)were randomly selected as controls. The HBs Ag-encoding gene was amplified and cloned, and at least 15clones per patient were sequenced and analyzed. Results The number of residue changes within the S protein group Ⅰ was 2.7 times more frequently than that in group Ⅱ patients, and "a" determinant of the major hydrophilic region(MHR)occurred mostly. Ten patients (71%)from group Ⅰ and three patients(25%)from group Ⅱ presented at least two residue changes in the MHR. The most frequent changes in group Ⅰ patients were located at positions s145,s129,s126,s144, and s123 as described for immune escape variants. Conclusions In CHB patients, the coexistence of HBsAg and HBsAb is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process play an important role in vaccine efficacy, diagnosis and clinical therapy.