Although glucocorticoids are known to attenuate vasopressin (AVP) secretion, it is still controversial whether glucocorticoids act on the hypothalamo-neurohypophysial system. We report here glucocorticoidal regulation of pituitary AVP content, which is a specific indicator for the system. The hypothalamic AVP mRNA content and the pituitary AVP content were measured in rats given dexamethasone (2 mg/kg, 2 times over the course of 5 d) or the glucocorticoid receptor antagonist RU-38486 (20 mg/kg, 3 times over the course of 3 d) during euhydration or dehydration. In dexamethasone-treated rats, both the hypothalamic AVP mRNA content and pituitary AVP content decreased after dehydration. In contrast, in the RU-38486 group the hypothalamic AVP mRNA content and pituitary AVP content increased in both euhydrated and dehydrated rats. These results suggest that glucocorticoids may act on hypothalamo-neurohypophysial vasopressinergic system and attenuate its activity under both basal and dehydrated states.