Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.