Abstract The large surface area of mucosal surfaces, particularly of the gastrointestinal tract, is protected against microorganisms and environmental antigens by various innate factors (e.g., mucins, lactoferrin, and others) and specific antibodies which are of IgA, or in some species, IgG Isotypes. Passive protection provided by effective prenatal transplacental transport of maternal antibodies and/or post-natal consumption of milk antibodies in breastfed newborns, is essential for the survival of neonates. Passive protection of mucosal surfaces by pre-formed antibodies in non-breast juveniles or adults is currently used only on an experimental basis: IgA-enriched preparations of gamma-globulin have been successfully given to children, and antibodies specific for several gastrointestinal pathogens have been isolated from immunized cows' milk, hens' eggs, or transgenic plants. Systemic administration of pre-formed antibodies is effective for protection against intestinal pathogens in species (e.g., mice, rats) endowed with efficient hepato-biliary transport of IgA into the gut lumen. However, this route of antibody administration is of limited efficiency in other species, including humans, in which almost all intestinal antibodies are produced locally by plasma cells in the gut mucosa and are not derived to a significant degree from the circulation. Active immunization is preferable for long-lasting protection. The site of immunization and presence of lymphoid tissues with inductive potential play an essential role in generating humoral immune responses in mucosal secretions. The relative efficiency of immunization routes (e.g., oral, nasal, rectal or genital) in the induction of preferential antibody responses in the intestinal secretion has not been studied extensively. Furthermore, suitable antigen delivery systems for achieving this goal must also be considered.