Considerable investigative effort is currently being directed towards the use of oral immunization for the prevention of mucosal infections, including otitis media, in infancy and childhood. The development of immune response to mucosally introduced vaccines or environmental antigens is significantly influenced by the mucosal microflora, enzymatic activity, factors influencing epithelial permeability and the nature of vaccine antigens administered. Studies carried out during the past several years have suggested that antigen uptake, antigen processing, and immune response to environmental antigens in the respiratory and intestinal mucosa are greatly altered by coexisting mucosal infections. High levels of ovalbumin or ragweed antigens were often observed in the serum associated with increased IgE-specific antibody responses following concurrent infection with respiratory syncytial virus, or rotavirus, respectively. The influence of the mucosal enzymatic environment has been recently evaluated after oral immunization with replicating poliovaccine or parenteral immunization with inactivated poliovaccines. High levels of neutralizing and VP3-specific antibody response and antibody activity against antigenic determinants generated in the intestine were observed characteristically after oral immunization with replicating virus. Such responses were conspicuously absent after parenteral immunization. These observations suggest that diverse elements of the mucosal microenvironment play an important role in the outcome of infections and development of immune responses at mucosal surfaces.