Compared with normotensive mucosa, the portal hypertensive gastric mucosa has increased susceptibility to injury by noxious agents such as alcohol and aspirin, but the mechanism of this phenomenon is unclear. Since the microvasculature of the normal gastric mucosa is an important target of injury by these agents, we studied the histologic and ultrastructural features of gastric vasculature and mucosal microvasculature in rats with portal hypertension (produced by staged portal vein ligation) and in sham-operated rats. In portal hypertensive rats, the gastric mucosa was swollen and hyperemic and the endothelial cells of mucosal microvessels had very prominent enlarged cytoplasm obstructing capillary lumina. Quantitative analysis of transmission electron micrographs demonstrated that in portal hypertensive rats the gastric mucosal capillary endothelium had significantly increased cytoplasmic area (236%), increased pinocytic vesicular area (416%) and increased capillary basement membrane thickness (143%) compared to respective parameters in sham-operated control rats. Arterioles in the muscularis mucosae and in submucosa were thickened, and submucosal veins demonstrated features of arterialization. All these findings indicate that portal hypertension produces definite microvascular changes in the gastric mucosa resulting in compromise of the capillary lumina. These changes may be the basis for the observed morphologic and functional abnormalities of the portal hypertensive mucosa and its increased predisposition to injury.