The successful prevention of infection with hepatitis B virus (HBV) has been achieved by vaccination with purified hepatitis B surface antigen (HBsAg). The ability of a novel synthetic HBV envelope antigen vaccine (Hep B-3, Hepagene; Medeva), which contains part of the pre-S1 and the complete pre-S2 regions and the whole of the S region and was produced in a mammalian cell line, to induce antibodies required for a protective immune response is of importance. In this study, the use of a panel of monoclonal antibodies known to bind to epitopes within the common "a" determinant has demonstrated that the epitopes present on this new vaccine are comparable to those found with plasma-derived HBsAg. In addition, the epitope specificity of the antibodies induced by this vaccine was examined and shown to accord well with previous results obtained using both a plasma-derived vaccine and a recombinant vaccine prepared in yeast.