Transgenic potatoes were engineered to synthesize a cholera toxin B subunit (CTB) pentamer with affinity for G,ganglioside. Both serum and intestinal CTBspecific antibodies were induced in orally immunized mice. Mucosal antibody titers declined gradually after the last immunization but were restored following an oral booster of transgenic potato. The cytopathic effect of cholera holotoxin (CT) on Vero celis was neutralized by serum from mice immunized with transgenic potato tissues. Following intraileal injection with CT, the plantimmunized mice showed up to a 60% reduction in diarrhea1 fluid accumulation in the small intestine. Protection against CT was based on inhibition of enterotoxin binding to the cellsur face receptor G,,,,ganglioside. These results demonstrate the abilii of transgenic food plants to generate protective immunity in mice against a bacterial enterotoxin.