Secretory IgA antibodies are heavily glycosylated, protease resistant, polymeric immunoglobulins. As the predominant antibody class in respiratory and gastrointestinal sections, sIgA represents a first line of defense against mucosal pathogens. Here we demonstrate that sIgA can function in both innate and acquired immunity to the shiga-like toxin ricin. Ricin, a member of the A-B family of toxins, is comprised of an enzymatic A subunit and a galatose-specific lectin B subunit. In solid phase binding assays, ricin bound to N- and O-linked oligosaccharide side chains on secretory component and the heavy chains of human IgA1 and IgA2, independent of the antibody variable domains. Ricin had no detectable affinity for human IgG. sIgA (but not IgG) reduced ricin attachment to the apical surfaces of polarized intestinal epithelial cells grown in culture and to the lumenal surfaces of human duodenum in tissue section overlay assays. These data indicate that oligosaccharide side chains on sIgA may serve as ‘decoy’ receptors for ricin, thereby reducing (but not completely eliminating) the effective dose of toxin that gains access to the intestinal epithelium. Furthermore, these results suggest that acquired immunity may be necessary to completely safeguard against toxin exposure in vivo. To test this we produced a panel of monoclonal IgA antibodies against the ricin A and B subunits. Although neutralizing antibodies against both toxin subunits were identified, only those directed against the B subunit completely prevented ricin attachment to sections of human duodenum. We are currently testing whether these antibodies are protective in an animal model of gastrointestinal ricin poisoning. While we assume that the formation of SIgA-ricin complexes in vivo will prevent the absorption of ricin by the intestinal tract, we have recently shown that Peyer’s patch M cells can mediate the uptake and transepithelial transport of sIgA (and possibly sIgA-antigen complexes). This raises the possibility that sIgA antibodies could actually promote the transport of a small amount of toxin from the intestinal lumen to underlying gut-associated leukocytes.