The purpose of this study was to examine whether increased vascular permeability contributes to the development of gastric mucosal lesions after intragastric administration of ethanol, and to know whether the cytoprotective effect of misoprostol, a kind of prostaglandin E, series, is mediated through the inhibition of changes of the vascular permeability. The degree of extravasation of intravenously injected Evans blue into the rat gastric contents and glandular stomach mucosa was used as an indicator of vascular permeability. Although minimal changes occurred in gross, light and electronic microscopic findings, the degree of extravasation of Evans blue 1 min after 75% ethanol exposure was significantly increased (18.4+3.3 mcg/ml of gastric contents, 24.1+5.6 mcg/100mg of tissue) than control (4.7+2.7 mcg/ml, 5.2+3.5 mcg/100 mg). However, pretreatment with misoprostol did not induce any significant vascular permeability (21. 3+7.0 mcg/ml, 14.6+3.3 mcg/100 mg). Therefore, it is suggested that increased vascular permeability is an early pathogenetic factor in ethanol induced gastric mucosal lesion. The mechanism of cytoprotective effect of misoprostol remains to be further elucidated.