We have developed a model of isochemic bowel necrosis in the rat by injecting platelet-activating factor (PAF) or PAF in combination with bacterial endotoxin. PAF causes profound hypotension, and it has been suggested that it is released during endotoxin shock. Because ischemic bowel necrosis is often associated with shock or infection, it is possible that PAF is the endogenous mediator that causes shock and bowel necrosis during sepsis. In this study, we have demonstrated that: 1) normal intestine contained a small amount of PAF; 2) necrotic lesions of the intestine could be induced by endotoxin injection; 3) PAF production in the bowel is markedly increased in animals treated with endotoxin; 4) pretreatment of the animal with PAF antagonists prevent endotoxin-induced necrosis; 5) isolated, buffer-perfused small intestine produced a small quantity of PAF in response to endotoxin injection. Therefore, we conclude that PAF is a likely endogenous mediator in endotoxemia, which causes bowel necrosis and shock.