Gastric mucosal perfusion is increased in portal-hypertensive gastropathy, and this may contribute to gastric bleeding from these lesions. Therefore drugs reducing gastric mucosal perfusion may be beneficial in the treatment of overt bleeding from portal-hypertensive gastropathy. In this study gastric mucosal perfusion was assessed in 28 cirrhotic patients with portal-hypertensive gastropathy under basal conditions and after double-blind intravenous administration of vasopressin (0.4 U/min), glypressin (2-mg injection) or placebo, with laser-Doppler flowmetry and reflectance spectrophotometry. Vasopressin and glypressin induced a significant increase in blood pressure and a decrease in heart rate. These effects were more pronounced in the vasopressin group. Both vasopressin and glypressin induced a sustained and similar reduction in gastric mucosal perfusion as assessed by laser-Doppler flowmetry (-36% +/- 8% and -34% +/- 6%, respectively; p < 0.05 with respect to basal values and with respect to the control group), whereas placebo had no effect. Both drugs significantly reduced the oxygen content of the gastric mucosa; however, the impairment in mucosal oxygenation was greater (p < 0.05) in the vasopressin group (-17% +/- 3%) than in the glypressin group (-6% +/- 0.1%). We conclude that the increased gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy may be reduced by either vasopressin or glypressin. These findings support the use of these drugs in clinical trials treating bleeding portal-hypertensive gastropathy. The lower reduction in gastric mucosal oxygen content observed with glypressin could decrease the incidence of ischemic adverse events associated with the use of vasopressin.