Platelet-activating factor (PAF) has been shown to induce gastro-intestinal damage similar to that evoked by endotoxin, suggesting that this mediator may be involved in the formation of gastrointestinal lesions observed in various pathologies. Thus, the effects of BN 52021, a specific PAF antagonist, were investigated in several experimental models of gastro-intestinal damage in rats. BN 52021 markedly reduced the gastric alterations and almost totally abolished the intestinal lesions induced by PAF. Similarly, BN 52021 reduced gastro-intestinal damage induced by endotoxin, but it afforded less protection against endotoxin-induced changes than those caused by PAF. This difference is probably due to the multicomponent activating effect of endotoxin. In the cold restraint stress model, BN 52021 decreased both gastro-intestinal lesions and the change in plasma transaminase level. The results presented in this paper confirm the role of PAF in gastro-intestinal damage induced by endotoxin but also suggest the involvement of this mediator in stress-induced lesions. PAF-antagonists could thus be of therapeutic use in such pathologies.