The oral immunogenic and adjuvant properties of cholera toxin (CT) and its nontoxic B subunit (CT-B) were assessed in swine. Both whole CT and CT-B are oral immunogens in swine and CT is relatively more potent. Oral administration of 100 μg of CT resulted in a greater immune response than 1 mg of CT-B as measured by anti-CT-B IgA, IgG and IgM in local (jejunum) and distant (oral cavity) mucosal sites, and in systemic sites including blood and spleen. Lower doses of CT were potent adjuvants for the response to CT- B, but did not induce detectable immunity alone. The predominant response to oral CT-B administered with CT was intestinally produced and secreted IgA, with about 2500 per 106 jejunal lamina propria cells producing anti-CT-B IgA in immunized animals. While CT is a potent adjuvant for CT-B, its ability to act as adjuvant for heterologous proteins is more restricted. 50 μg of CT in combination with 1 mg of CT-B did not induce antibodies to 25 mg of coadministered KLH. However, chemical linking of ovalbumin to CT-B and coadministration with CT resulted in a detectable antibody response to ovalbumin. These results suggest that CT is immunogenic and is a potent adjuvant for CT-B in swine and that the induction of mucosal immunity to heterologous antigens may require specific targeting to the gut-associated lymphoid tissues.