The effect of cholera toxin, a potent mucosal adjuvant, upon the murine immune response to both soybean meal, a regular dietary antigen, and ovalbumin, a simulated dietary antigen, was examined. Mice were orally immunized with a target antigen, Sendai virus, with and without cholera toxin as a mucosal adjuvant. Both serum and intestinal IgA and IgG anti-Sendai virus antibody responses were significantly increased when cholera toxin was used. For soybean meal, the major protein source in laboratory animal chows, however, no increases in serum antibody titers were found in animals which received oral cholera toxin plus virus. In addition, in mice orally immunized with ovalbumin plus cholera toxin (and virus), both serum and intestinal IgA and IgG antibody titers against ovalbumin were increased. Oral pre-immunization with ovalbumin prior to oral ovalbumin plus cholera toxin, however, resulted in no increase in either serum or intestinal anti-ovalbumin antibody responses. Thus, the use of cholera toxin as an oral adjuvant does not increase antibody responses against dietary antigens if there has been pre-exposure to the dietary antigen.