Adhesion of gonococci to mucosal epithelial cells appear to be a critical step in the pathogenesis of gonococcal infection. Parameters affecting adhesion, the antigens involved in adhesion and the human antibody response that blocks adhesion have been studied. Gonococci adhere to a variety of human cells grown either in tissue culture or organ culture or scraped from mucosal surfaces. They adhere in greatest number to mucosal cells derived from sites of natural infection but buccal mucosal cells were used for most of these studies because of the ease of obtaining them, the homogeneous population obtained, and the similarity of the results of antibody studies with all cell types. The ability of a given strain of gonococci to attach to buccal cells (receptors) varied with the individual from whom the cells were obtained, and the capacity to support adhesion of a given strain fluctuated from day to day. The principal antigens mediating attachment are pili (filamentous protein appendages extending from the bacterial cell wall) which are antigenically heterogeneous. Lipopolysaccharide also blocks attachment but it is less efficient than pili and is not species-specific. Other antigens, probably proteins, also block attachment. Human antibody (both local and humoral) blocked the adhesion of gonococci. The antibody was directed against pili and the antigens in naturally occurring disease and could be induced by immunizing subjects with purified pili. The results of these studies suggest two new approaches to the prevention of gonorrhoea: (1) (competitive) inhibition of the adhesion with specific antigens, i.e. pili; and (2) immunization with purified attachment antigens to produce shielding antibodies.