Corticotropin-releasing hormone (CRH) and vasopressin (AVP) participate in the endocrine, autonomic, immunological and behavioral response to stress. CRH and AVP receptors are found in hippocampus and anterior pituitary, where mineralocorticoid (MR) and glucocorticoid (GR) receptors are abundant. We investigated the possible influence of CRH and AVP on the regulation of MR and GR in both tissues. CRH, AVP, or their antagonists were administered to adrenalectomized rats substituted with corticosterone, to avoid interference with adrenal secretion. Repeated i.c.v. oCRH injections (10 microgram) for 5 days significantly decreased MR and GR mRNA in hippocampus and MR mRNA in anterior pituitary. AVP significantly increased both corticosteroid receptor mRNAs, as repeated i.c.v. injections (5 microgram) for 5 days in hippocampus, and as continuous i.c.v. infusion (10 ng/h/5 days) in anterior pituitary. The i.c.v. infusion of 5 or 10 microgram/day of the alpha-helical CRH antagonist during intermittent restraint stress (5 days), induced a significant decrease in hippocampal MR binding. In anterior pituitary, 5 microgram/day significantly decreased MR binding, while 10 microgram/day significantly increased GR binding. Under the same conditions of stress, the infusion of 15 microgram/day of the vasopressin V1a/1b receptor antagonist [dP Tyr (Me)(2)AVP] significantly increased MR and GR binding in hippocampus and anterior pituitary; 5 microgram/day significantly decreased pituitary MR binding. Our results show that CRH and AVP regulate MR and GR in hippocampus and anterior pituitary. This reveals another important function of CRH and AVP, which could be relevant to understand stress adaptation and the pathophysiology of stress-related disorders like major depression.