Gastric mucosal lesions are an important complication in endotoxemia. In order to define the role played by the vagus nerve and endothelial-derived relaxing factor (EDRF) in gastric mucosal blood flow, an investigation was carried out on four groups of rats: a control group; a group given lipopolysaccharide (LPS, 5 mg/kg); a group given gossypol-acetic acid (gossypol), which has an injurious effect on the vascular endothelial cell; and a group given L-NG-monomethyl arginine (LNMMA). Following the administration of acetylcholine and papaverine hydrochloride (via the splenic artery) and vagus nerve stimulation in all four groups of rats, the effects of vagus nerve stimulation and EDRF on the gastric mucosal blood flow were determined with a laser Doppler rheometer. In the LPS group, the gastric mucosal blood flow was decreased after acetylcholine administration and vagus nerve stimulation. This was also the case in the gossypol group. These findings suggest that inhibition of EDRF release may be responsible for the reduced gastric mucosal blood flow observed in endotoxemia.