Hypothalamo-pituitary-adrenal (HPA) system dysfunction is the most characteristic biological alteration found in a majority of depressed patients. Accumulating evidence suggests that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA system abnormalities. The aim of this study was to evaluate whether the DEX/CRH test has a predictive value for the risk of depressive relapse in outpatients who are in clinical remission from a major depressive episode. Thirty-eight depressed outpatients (23 women, 15 men) in remission (MADRS score < or =8) underwent the DEX/CRH test and were followed up for 12 months regarding the occurrence of a new depressive episode. In parallel we recruited 24 controls (13 men and 11 women). The main result is a statistically significant difference concerning the delta and AUC numbers for cortisol plasmatic values between the group of patients who relapsed during the 1-year follow-up and control subjects, but not between the group of patients with prolonged remission and controls. These results suggest that in outpatients who are in clinical remission from a major depressive episode, high delta and AUC values in the DEX/CRH test compared to controls subjects can be associated with a higher risk of relapse.