Monoclonal antibodies were raised against hepatitis B core antigen (HBcAg) synthesized in Escherichia coli. They identified a single immunodominant determinant on both liver-derived and E. coli-derived HBcAg. Cross-inhibition studies demonstrated that HBsAg-containing human sera which contained antibodies to HBcAg (anti-HBc) together with either hepatitis B e antigen (HBeAg) or its antibody (anti-HBe) essentially only recognised the same single determinant as the murine antibodies. The identification of a single dominant HBcAg determinant may be important if future hepatitis B virus vaccines contain HBcAg.