Although over 90% of all human infections begin at a mucosal site (respiratory, gastrointestinal, urogenital, or ocular), the total number of infections occurring in the population is relatively low. This is in part the result of the secretion of a complex array of local and systemically produced immunoglobulins (Igs). Since the time of Pasteur (37), when immunization by the oral route was first described, and the identification of a special mucosal immune system by Besredka (7), considerable progress in understanding secretory immunity in humans has been achieved. Mechanisms of induction, synthesis, translocation, and activity of secretory immunoglobulin A (S-IgA) antibodies are now well established, as extensively reviewed in a recent book (46). However, while it would be more effective to block infections at the mucosa by using specific mucosal vaccines, the only such vaccine commercialized for human use is the oral polio vaccine (53). This delay in commercialization is due to the necessity of optimizing safety and efficacy which are related to a number of factors such as the requirements for persistent antigens (Ags) which linger on mucosal surfaces, for highly effective mucosal adjuvants, and for live mucosal vaccine vectors with harmless colonizing properties. Present efforts have focused on the study of both mucosal adjuvants, mainly cholera toxin and its derivatives, and immunogens such as encapsulated molecules, DNA, and recombinant microorganisms. Alternatively, an understanding of additional aspects of antibody-mediated immunity in secretions may enable us to develop new methods of local protection against pathogens. We present here those immune mechanisms known to be used by the host to block infection at the mucosal surface and discuss their respective importance and limitations.