Both arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) are involved in the release of ACTH in man. Desmopressin (DDAVP), a synthetic analogue of AVP, has been shown to have a CRH-like action (able to promote ACTH and cortisol release) in animals but not in normal man. Nevertheless, DDAVP is able to release ACTH and cortisol in ACTH-dependent Cushing's disease. We studied eight anorexia nervosa (AN) patients [as AN is a condition in which chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly reported] in a refeeding phase of the disease, to evaluate whether, after weight gain, ACTH and cortisol response to ovine corticotropin-releasing hormone (oCRH) [1 microgram i.v. DDAVP alone and as pretreatment to oCRH (1 microgram kg-1 BW i.v.)-induced secretion of ACTH and cortisol. We studied six normal women as control subjects. No significant differences in ACTH and cortisol responses to oCRH were found between AN patients and control subjects. DDAVP was not able to stimulate ACTH or cortisol release in AN patients or in control subjects, but in the latter it was able to significantly enhance (P < 0.05) ACTH [area under curve (AUC): 590.0 +/- 104.4 pmol L-1 120 min-1] and cortisol (AUC: 28899.0 +/- 6935.2 nmol L-1 120 min-1) responses to oCRH (ACTH AUC: 325.7 +/- 101.7 pmol L-1 120 min-1, cortisol AUC: 14197.4 +/- 2930.0 nmol L-1 120 min-1). The present data show that DDAVP does not stimulate ACTH and cortisol in AN patients or, as previously reported, in normal subjects. However, DDAVP is able to enhance ACTH and cortisol release after oCRH administration in normal subjects but not in AN patients. This finding could be due to a down-regulation of hypophyseal DDAVP V3 receptors in AN as a direct consequence of the hypercortisolaemic status usually present.