The heat-labile enterotoxins expressed by Vibrio cholerae (cholera toxin) and Escherichia coli (LT-I, LT-IIa and LT-IIb) are potent systemic and mucosal adjuvants. Coadministration of the enterotoxins with a foreign antigen produces an augmented immune response to that antigen. Although each enterotoxin has potent adjuvant properties, the means by which the enterotoxins induce various immune responses are distinctive for each adjuvant. Various mutants have been engineered to dissect the functions of the enterotoxins required for their adjuvanticity. The capacity to strongly bind to one or more specific ganglioside receptors appears to drive the distinctive immunomodulatory properties associated with each enterotoxin. Mutant enterotoxins with ablated or altered ganglioside-binding affinities have been employed to investigate the role of gangliosides in enterotoxin-dependent immunomodulation.