Neutralizing antibodies induced by immunization against hepatitis B infection are targeted to the conformational epitopes of the common a determinant of the surface antigen. However, amino acid substitutions within this region of the surface protein of the virus, particularly in the region of amino acid 137-147 allow replication of hepatitis B virus in vaccinated subjects, since antibodies induced by current vaccines do not recognize crucial changes in the surface antigen domain. The G145R mutant is replication competent and is stable, and it appears to be the most common variant. There is evidence that these mutants may not be detected by current screening tests and diagnostic reagents. Epidemiological monitoring of hepatitis B virus surface mutants is essential.