Pre-S2 region (amino acids 120-174) of hepatitis B virus surface antigen contains immunodominant and disulfide bond-independent epitopes. Using pre-S2 peptides (recombinant peptides 121-174/adw2, 134-170/adw2 and synthetic peptide 120-145/ayw), epitope and polyalbumin receptor region on pre-S2 were studied. Polyalbumin receptor assay and enzyme immunoassay provided evidences that the region of at least 12 residues (134-145) of pre-S2 was shared by epitope for an anti-pre-S2 monoclonal antibody and polyalbumin receptor. This region was shown to be hydrophilic and a possible β-sheet.