The ganglioside preventing the action of cholera toxin in the rabbit skin and on the adenyl cyclase system in the small intestine of the guinea pig has been identified as the sialidase-resistant monosialosylganglioside known as G_M1or GGnSLC. Sialidase-sensitive di- and trisialosylgangliosides, including the tetanus toxin-fixing gangliosides G_D1b and G_T1 (GGnSSLC and SGGnSSLC), do not react with cholera toxin. Treatment of these gangliosides with sialidase or weak acid renders them capable of deactivating cholera toxin. Similar treatment of intestinal mucosal scrapings greatly increases their capacity to deactivate cholera toxin. The nature of the toxin receptor in the small intestine possibly suggests that the sialidase of Vibrio cholerae may be relevant to the development of cholera.