The class 4 protein of Neisseria meningitidis is a highly conserved outer membrane protein, closely related to the protein PIII of Neisseria gonorrhoea. Monoclonal antibodies SM50 and SM54 raised against PIII also react with class 4 protein but do not promote complement mediated bactericidal killing of meningococci. In addition, mAb SM50 inhibits the anti-meningococcal bactericidal activity both of normal human sera and of mAb SM300, directed against a protective epitope on the class 1 outer membrane protein. The ability of class 4 protein to induce such 'blocking' antibodies suggests that its presence in experimental vaccines, based on meningococcal outer membranes, may be antagonistic to the development of effective bactericidal immunity.