PROBLEM: Consistent with the absence of protective immunity resulting from previous infection with Neisseria gonorrhoeae, the genital mucosal immune response in human gonorrhea is weak: only low levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies an detectable against gonococci, and inflammatory cytokine responses are poor. METHOD OF STUDY: Mucosal immunization strategies designed to induce persisting genital antibody responses might afford protection against infection, if appropriate conserved antigens can also be identified. RESULTS: Intragastric or intranasal immunization with bacterial antigens expressed as recombinant chimeric proteins with cholera toxin A2/B subunits induced persisting IgA antibodies in genital and other secretions, and circulating IgG antibodies. CONCLUSION: Although gonococci may avoid inducing or even suppress immune responses during natural infection, alternative approaches to vaccine development may be successful. However, inadequate understanding of the origins of antibodies in the genital tract, and their effector mechanisms, will need to be rectified to make this possible.