Pure cholera toxin (CT) given as a booster in enteric-coated tablets to rats produced a humoral and intestinal immune response similar to the result of instilling the boosting dose of CT directly into the duodenum. This method protects the antigen against gastric acid and allows delivery of the immunogen to intestinal mucosa, an essential step in producing intestinal secretory IgA. Immunization gave protection against pure CT during intestinal perfusion but also significantly protected against the secretory effects of E. coli LT and CT-like toxin of A. sobria. The use of enteric-coated vaccines offers advantages for mass immunization programmes and our results suggest that immunization with preparations containing CT holotoxin may protect against heterologous toxins which cross-react with CT.