Glucocorticoid hormones produced in response to various ulcerogenic stimuli contribute to the maintenance of the gastric mucosal integrity. The role of glucocorticoids in gastroprotection becomes especially important where there is deficiency of prostaglandins (PGs) or nitric oxide (NO) or desensitization of capsaicin-sensitive sensory neurons (CSN). It has been found that neither inhibition of PG or NO production nor desensitization of CSN by itself provokes damage in the gastric mucosa of rats with normal corticosterone levels. However, each of these treatments results in mucosal damage in adrenalectomized rats; this effect being prevented by corticosterone replacement. Indomethacin-induced gastric erosions are potentiated to similar degrees by adrenalectomy, inhibition of NO production or desensitization of CSN. The potentiation caused by inhibition of NO production or CSN desensitization is further enhanced by concomitant glucocorticoid deficiency. These results suggest a pivotal compensatory role of glucocorticoids in the maintenance of the gastric mucosal integrity under the adverse conditions where the gastroprotective mechanisms provided by PGs, NO and capsaicin-sensitive sensory neurons are impaired.