In the rat, stress activates the hypothalamus inducing central sympathetic discharge and delivery of alpha-adrenergic stimulation to the stomach by the adrenergic hypothalamovagal pathway. This stimulation controls intragastric blood flow and 5-HT release. Administration of reserpine produces stress pharmacologically and stimulates the mentioned pathway. Six hours after intraperitoneal reserpine (5 mg/kg), gastric mucosal lesions are produced in all rats. These lesions are vascular in origin and do not require gastric acid or duodenal contents for their development. However, reflux of duodenal contents into the stomach is associated with this pathway stimulation and increases lesion severity. Stimulation of the pathway with a single intraperitoneal injection of reserpine (5 mg/kg) every 24 h for five days produces chronic gastric ulceration in 80% of rats demonstrating the relationship between stress and chronic gastric ulceration. In addition it is observed that the duration of stress in the rat determines the nature of the gastric lesion produced.