This report reviews the immunophysiology of the mucosal immune system, the principal antibody of which is a special form of IgA, termed secretory IgA. This IgA is produced locally by mucosal plasma cells that are descended from precursors initially stimulated in organized, mucosal lymphoid organs designed for antigen sampling. After the initial triggering, the precursor cells pass via regional lymph nodes, lymph, and blood to disseminate widely among mucosal sites. After secretion from a local plasma cell, IgA binds to an epithelial cell surface receptor and the complex passes through the epithelial cell into the secretions where it serves as a nonphlogistic immunologic barrier to inhibit uptake of antigens. The production of IgA is facilitated by particular regulatory T cells. At the same time, the synthesis of other classes of antibody, such as the phlogistic IgG, is dampened. This differential regulation of individual antibody classes after exposure to mucosal antigen plus the interrelatedness of the various mucous membranes of the body have important implications for host defense, pathogenesis of a variety of diseases including IgA nephropathy, and strategies of immunization.