The portal of entry for most pathogens is at the mucosal surface, and mucosal defences afford the host the earliest opportunity to ward off infection. The vagina is exposed to considerable trauma, and harbours a complex microflora, but only a small number of microorganisms are associated with disease. It seems likely that mucosal defenses are important in this process. Mucosal secretions contain mucus, lysozyme, lactoferrin, zinc, fibronectin, and complement, all of which afford non-specific protection. In addition, secretory immunoglobulin A (IgA) concentration in these secretions increases in response to specific pathogens. Blood leukocytes migrate onto mucosal surfaces during infection with some microorganisms, and the interaction between phagocytic cells and genital pathogens has been the focus of intense investigation. Improved understanding of mucosal defences is crucial for prevention of infection.