Clostridium perfringens enterotoxin (CPE), a single polypeptide of approximately 35 kDa in size, is -associated with type A food poisoning and such non-foodborne gastrointestinal diseases as antibiotic-associated diarrhea and sporadic diarrhea. CPE action begins with binding of the toxin to a claudin -receptor, forming a ∼90 kDa small complex that then rapidly oligomerizes into a hexamer of ∼450 kDa termed CH-1 (CPE hexamer-1). CH-1 is essentially a pore through which calcium gains entry to the cytoplasm, altering cell permeability and resulting in cell death by oncosis or apoptosis. Additionally, tight junctions are disrupted, allowing CPE access to the basolateral membrane so it can produce additional CH-1 -complexes and also the CH-2 complex (∼600 kDa) that contains occludin. We have recently demonstrated the presence of claudins-3 and -4 in both the CH-1 and CH-2 CPE complexes formed after CPE treatment naturally sensitive Caco-2 cells. Interestingly, claudin-1, which binds CPE poorly (if at all), was also present in these complexes.