The heat-labile enterotoxins (HLT) of Vibrio cholerae and Escherichia coli constitute a family of bacterial toxins that are related in structure and function (10,11,16,35). Both are oligomeric protein toxins composed of one A polypeptide and five B polypeptides in which the quaternary structure is maintained by noncovalent bonds between the A polypeptide and a pentameric ring of B subunits (7,13,32). The biological effects of the enterotoxins are determined by the binding specificity of the fully assembled B subunits and the enzymatic activity of the A subunit. The pentameric ring formed by the B subunits mediates binding to the sugar residues of gangliosides present on the surface of various eukaryotic cells (3,18).Two serogroups of HLT have been distinguished on the basis of distinct immunoreactivity (15, 28). Serogroup I consists of cholera toxin (CT) and the E. coli HLT LT-I, which includes two antigenic variants isolated from humans and pigs, designated respectively (19,28). Serogroup II enterotoxins include E. coli type II HLT initially designated LT-like toxins and later called LT-II enterotoxins (9). Based on immunoreactivity and amino acid sequence homology, two antigenic variants of LT-II, designated LT-IIa and LT-IIb, have been isolated (9)(10)(11)17). Although serogroup I and serogroup II enterotoxins induce similar morphological effects on Y1 adrenal cells and activate adenylate cyclase in cell cultures, both LT-IIa and LT-IIb appear to be more potent than either CT or LT-I in Y1 adrenal cell assays; however, neither LT-IIa nor LT-IIb induces the typical fluid accumulation in ligated ileal loops observed with CT and LT-I (16). In human T84 intestinal cells, only CT elicited a cyclic AMP-dependent chloride response that is responsible for the massive effusion of water into the lumen of the gut (39).Comparison of the predicted amino acid sequences of type I and type II enterotoxins reveals a large degree of variability. While the B polypeptides of CT and LT-I exhibit over 80% homology to each other, both CT and LT-I have less than 14% amino acid sequence homology to the B subunits of either LT-IIa or [28][29][30]. The extensive diversity in amino acid sequences between type I and type II HLT not only results in antigenically distinct groups but also imparts different ganglioside binding specificity to the respective B subunits. Specifically, the high-affinity receptor for CT and LT