Pure enterotoxins from two strains of Vibrio cholerae and choleragen-related heat-labile enterotoxins (LTs) from strains of Escherichia coli of human and porcine origin were examined by Ouchterlony-type immunodiffusion assays and by neutralization tests in Y-1 adrenal cells using specific and immunopurified antisera. In accordance with previous findings, the results indicated that each of the toxins shared antigens with each of the others and that each, in addition, possessed unique antigenic determinants. The present study, however, indicates further that enterotoxin-type specific antibodies, in some instances, account for a major portion of the neutralizing activity. The full extent and importance of the antigenic drift in the cholera/coli family of ADP-ribosylating, adenylate cyclase-activating, heat-labile enterotoxins remains to be determined. The results will be pertinent to efforts to develop broad-spectrum antitoxic immunity as well as in the development of methods for the rapid detection and identification of enterotoxigenic strains.