The dexamethasone suppression test (DST), frequently abnormal in mood disorder patients, is considered to measure glucocorticoid receptor-mediated negative feedback. We examined the hypothesis that the, apparently more sensitive, dexamethasone/corticotrophin-releasing-hormone (dex/CRH) test unveils subtle hypothalamic-pituitary-adrenal axis disturbance not detected by the DST in 82 patients with mood disorders and 28 controls. There was a close correlation between the cortisol responses on the two tests (r(s)=0.73, p<0.0005). However, ROC analysis revealed that the dex/CRH test had better diagnostic performance than the DST (p=0.031). The sensitivity of delta cortisol (from the dex/CRH) was 61.9% and the specificity 71.4%. The sensitivity of 1500 h cortisol (the DST) was 66.6% and the specificity was 47.6%. This suggests that the two tests measure common pathology but that the dex/CRH test has better diagnostic utility.