Abstract The vast majority of infectious diseases of animals and humans occur at mucosal surfaces, especially in the intestinal tract. However, vaccines to stimulate durable immunity to intestinal pathogens often do not produce effective protection. A better understanding of the molecules and molecular mechanisms that mediate effective immune induction at mucosal surfaces may facilitate the development of more effective mucosal vaccines. Characterization of the mRNA expression profile of Peyer's patch, a key immunological tissue in immune surveillance and response, would help to identify important proteins and pathways required for the development of effective mucosal immunity in swine. We produced a cDNA library of about 2400 genes differentially expressed in jejunal Peyer's patch, of which approximately 900 had unknown functions or were novel to public databases. We hypothesize that knowledge of the roles and regulation of the encoded proteins under conditions of substantial immune stimulation will help to understand mucosal immunoregulatory mechanisms in the Peyer's patch. Cholera toxin is a potent mucosal adjuvant and antigen. The response to cholera toxin is amenable to dissection at a variety of levels from local to systemic and molecular to cellular in whole animals, tissue explants, and cultured cells. The powerful tools of genomics and genetics that are now available provide veterinary immunologists with new opportunities to elucidate and dissect the mysteries of host defense. By building on the findings from multiple systems and models we can develop a better understanding of complex interactions of immune and absorptive tissues in the regulation of immunity in the small intestine.