This chapter discusses those sexually transmitted diseases (STDs) that predominantly infect the genital mucosae. Neisseria gonorrhoeae is an exclusively human pathogen. Symptomatic or asymptomatic gonococcal infections may occur at virtually any mucosal site exposed through sexual contact. The Gonococcal infections usually remain localized to the sites of primary infection, most often the male urethra or female cervix, or they spread to contiguous structures to cause complications such as-pelvic inflammatory disease (PID) or epididymitis. The initial step in gonococcal pathogenesis, adherence to epithelial cells, is primarily determined by pili and Opa-which bind specific receptors. CD46 is the receptor in the case of pili, and either glycosaminoglycans or CEACAM family members in the case of Opa. Gonococcal antigenic variation (by porin and to a greater degree by pilin and Opa proteins) is itself an approach for dissipating an immune response against a vast array of epitopes, in effect exploiting the phenomenon of "antigenic competition.". © 2005 Elsevier Inc. All rights reserved.