The hypothalamic-pituitary-adrenocortical system is a hormonal component of brain-gut axis. There are two opposite points of view regarding the influence of stress-induced activation of hypothalamic-pituitary-adrenocortical system on the stomach. According to the widely held view, glucocorticoids released during stress are ulcerogenic hormones and, therefore, stress-induced activation of hypothalamic-pituitary-adrenocortical system is harmful. The results of our investigations are, however, opposite to this traditional view. To estimate the action of glucocorticoids released during stress on the gastric mucosa, the effects of glucocorticoid deficiency or occupation of glucocorticoid receptors by the antagonist RU-38486 on the formation of stress-induced gastric erosions were estimated in rats. The reduction of stress-induced corticosterone release (induced by various experimental approaches) markedly potentiated a gastric erosion formation caused by stress and acute corticosterone replacement, mimicking stress-induced corticosterone response, prevented this erosion-potentiating effect. The administration of RU-38486 also caused a significant increase of vulnerability of gastric mucosa to stress action. Thus, an acute stress-induced increase of glucocorticoids has a gastroprotective action against stress-induced gastric injury. We also showed that various ulcerogenic stimuli, similar to stress, induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Gastroprotective action of glucocorticoids may be mediated by multiple actions, including maintenance of glucose homeostasis, gastric mucosal blood flow, mucus production and attenuation of enhanced gastric motility and microvascular permeability. For maintenance of gastric mucosal integrity glucocorticoids may cooperate with prostaglandins. In conclusion, these findings indicate that activation of hypothalamic-pituitary-adrenocortical system could be considered as a significant gastroprotective component of brain-gut axis.