Peptic ulcer in the human stomach causeslocalized destruction of the gastric wall, which may beassociated with focal vascular insufficiency.Endothelin-1, an extremely potent vasoconstrictorpeptide, modulates regional blood flow in thevasculature of stomach, suggesting a role forendothelin-1 in peptic ulcer. We examined therelationship among endogenous plasma and mucosalendothelin-1 concentrations and the severity and area of ulcer in 19patients with gastric ulcers and eight healthy adults.Endothelin-1 concentrations were measured by enzymeimmunoassay in plasma and gastric mucosal specimens from ulcer margins, corpus, and antrum. The severityand area of ulcer were assessed endoscopically. Plasmaendothelin-1 concentrations in active (P < 0.01compared with normal) and healing (P < 0.05) stagesof ulcer were significantly greater than those innormal subjects. Plasma endothelin-1 concentrations, butnot mucosal endothelin-1 concentrations in the ulcermargin, were significantly associated with the severity of the ulcer. There was a significantpositive correlation between plasma endothelin-1concentration and area of ulcer (r = 0.70, P < 0.01).In conclusion, locally increased endothelin-1 may be an important mediator contributing to thepathogenesis of peptic ulcer.