Clinical studies have demonstrated the efficacy of submucosal epinephrine injection in the control of bleeding ulcers. Since endoscopic techniques for assessing gastroduodenal blood flow are limited, we employed an animal model to study the mechanism of control of bleeding. The effect of submucosal epinephrine injection on local gastric blood flow was studied in the rat using laser Doppler flowmetry and reflectance spectrophotometry. Submucosal injection of 0.1 ml of 1/10,000 epinephrine caused a significantly greater drop in local gastric blood flow (laser Doppler flowmetry) compared with vehicle (10% sodium metabisulfite) injection. The reduction persisted for up to 120 min. This vasoconstrictive effect of epinephrine was confirmed by observations with reflectance spectrophotometry, which documented a pattern of ischemia without congestion (lower index of hemoglobin concentration, lower index of oxygen saturation). The autoregulatory escape from adrenergic vasoconstriction was not evident in either instance. We conclude that, after submucosal injection of epinephrine, the absence of autoregulatory escape from adrenergic vasoconstriction and the marked and prolonged decrease in local gastric blood flow enhance the homeostatic mechanisms (eg, platelets and other coagulative factors) to effect hemostasis in bleeding ulcers.