This article presents an analysis of data providing evidence of the important contribution of the hypothalamo-hypophyseal-adrenocortical system (HHACS) to the processes maintaining the integrity of the gastric mucosa. According to these data, glucocorticoid hormones produced during stress-induced activation of the HHACS are gastroprotective hormones rather than ulcerogenic factors, as is widely believed. The gastroprotective influence of glucocorticoids has been demonstrated on exposure to ulcerogenic stimuli of different modalities. The gastroprotective action of glucocorticoid hormones is mediated via type II glucocorticoid receptors and may be associated with the maintenance of the blood glucose level, their calming effects on pathogenetic factors, and their favorable effects on protective factors for the gastric mucosa. Glucocorticoid hormones can compensate for the absence of the gastroprotective action of prostaglandins, nitric oxide, and capsaicin-sensitive neurons. The data lead to the conclusion that activation of the HHACS is an important gastroprotective component of the stress reaction.