The effects of endotoxic shock on the synthesis of PAF-acether by the stomach, duodenum and lung were examined in the rat. Furthermore, the effect of pretreatment with prostaglandin E2 on endotoxin induced PAF-acether synthesis and changes in vascular permeability were examined. Administration of endotoxin resulted in significant increases in PAF-acether synthesis in all tissues studied. Such increases were apparent within 5-15 minutes of the administration of endotoxin, corresponding to the time when significant hypotension, hemoconcentration and increases in gastrointestinal vascular permeability were first observed. Pretreatment with prostaglandin E2 resulted in a significant reduction of endotoxin-induced hypotension, hemoconcentration and changes in vascular permeability in the gastrointestinal tract. However, prostaglandin pretreatment did not significantly alter endotoxin-induced PAF-acether release from the gastrointestinal tissues studied. These results demonstrate that prostaglandin E2 can significantly attenuate several of the systemic and gastrointestinal manifestations of endotoxic shock. The mechanism responsible for these beneficial actions appears to be unrelated to effects of prostaglandin E2 on PAF-acether synthesis.