The NetF toxin found in type A C. perfringens is a recently discovered toxin which is a member of the beta-pore-forming toxin leucocidin-hemolysin family, an important group of clostridial necrotizing toxins (Figure 9.1). The toxin was designated NetF for several reasons: it belongs to the same family of toxins as the relatively recently described NetB, associated with necrotic enteritis of chickens; it is associated with disease in foals (hence the “F”); and the strains could be considered to be “type F” if the current classification of C. perfringens as types A–E is to be expanded. C. perfringens strains producing NetF also produce another closely related toxin called NetE; both are encoded on the same large plasmid, whereas the enterotoxin (CPE) and often the beta2 toxin (CPB2) are encoded on a separate large plasmid, sometimes in conjunction with another, similar toxin called NetG. Analysis of the upstream region of these net genes has shown the presence of potential VirR boxes in the promoter region of netE and netG, but not of netF. VirR is a critical regulator of virulence in C. perfringens. An equine ovarian cell line has been found to be most susceptible to NetF, with canine cell lines the next most susceptible cells. Unlike NetF, NetE and NetG do not seem to have toxic activity, but they are expressed in vitro. Interestingly, since all NetF-producing strains also encode CPE, there may be a synergistic pathogenic effect in the intestine of NetF and CPE, as has been described for beta toxin (CPB) and CPE in rabbits.