Baseline 8 a.m. adrenocorticotropic hormone (ACTH) and cortisol levels and the postdexamethasone ACTH/cortisol values at 8 a.m. and 4 p.m. were determined in 86 depressed females diagnosed using DSM-III criteria. Postdexamethasone ACTH and cortisol values were significantly correlated with their baseline levels. We have shown that regression analysis should be used to assess dexamethasone-induced changes as the residual ACTH and cortisol responses, with the relative effects of the baseline data on the hormone responses being partialed out. The residual ACTH and cortisol values were significantly increased in the most severely depressed females as compared to minor depressives. The residual ACTH responses were markedly correlated with the residual cortisol responses. Cortisol nonsuppression during a depressive episode appeared to be determined by an augmented ACTH escape from dexamethasone suppression. The residual ACTH and cortisol responses could prove to be the most sensitive reflection of the disorder in the negative feedback by dexamethasone on the pituitary. In clinical practice, the ratio ln (postdexamethasone ACTH): ln (basal ACTH) can be used, since this ratio is linearly correlated with the residual ACTH responses.