Transepithelial transport of antigens by M cells in the epithelium associated with lymphoid follicles in the intestine delivers immunogens directly to organized mucosal lymphoid tissues, the inductive sites for mucosal immune responses. We have exploited M cell transport to generate and characterize specific monoclonal IgA antibodies that can prevent the interaction of pathogens with epithelial surfaces. The relative protective capacities of specific monoclonal IgA antibodies have been tested in vivo by generation of hybridoma tumors that result in the secretion of monoclonal IgA into the intestine. Using this method, we have established that the secretion of IgA antibodies recognizing a single surface epitope on enteric pathogens can provide protection against colonization or invasion of the intestinal mucosa.