Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses. CPE has a unique four-step membrane action that apparently involves: (1) CPE binding to a 50,000 mol. wt mammalian protein receptor, forming a small complex of 90,000 mol. wt; (2) the development of a post-binding physical change to this small complex; this physical change could represent either the insertion of CPE into the membrane or a conformational change to small complex; (3) an interaction between this physically changed small complex and a 70,000 mol. wt mammalian protein, forming a large, 160,000 mol. wt complex in membranes; and (4) a breakdown in normal plasma membrane permeability properties for small (< 200,000 mol. wt) molecules. Structure-function analyses have identified a receptor binding region at the C-terminus of CPE and indicate that residues in the N-terminal half of CPE are required for the second step in CPE action to occur. Finally, cpe genetic studies are in their infancy but already indicate that cpe can be either chromosomal or plasmid-borne and that only a tiny minority of the global C. perfringens population is cpe positive. CPE expression appears to be transcriptionally regulated during sporulation, at least in part, by regulatory factors that are common to all C. perfringens isolates.