The authors investigated the possibility of enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD) by using a low dose of dexamethasone. Baseline blood samples were obtained at 8: 00 am, and 0.5 mg of dexamethasone was administered to 21 male patients with PTSD and 12 normal age-comparable men at 11: 00 pm Cortisol and dexamethasone levels were measured 9 and 17 hours after dexamethasone administration. After correction for differences in dexamethasone levels, the PTSD patients showed greater suppression of cortisol in response to dexamethasone than did the normal subjects. This was true even in patients meeting con current diagnostic criteria for major depression. The data support earlier studies showing that HPA abnormalities in PTSD are different from those seen in depression and suggest that the low-dose dexamethasone suppression test may be a potentially useful tool for differentiating the two syndromes and further exploring differences in their pathophysiology.