The dexamethasone suppression test has been carried out in 111 depressed inpatients. Fasting, 8 a.m. plasma levels of Cortisol and adrenocorticotropic hormone (ACTH) were determined before and after administration of 1 mg dexamethasone. In 64 subjects multisequential (1-17,1-24,1-39) ACTH, and in 47 subjects intact (1-39) ACTH has been determined. Patients with melancholia exhibited significantly higher postdexamethasone Cortisol and intact ACTH values as compared with minor and simple major depressives. Severity of illness was significantly and positively related to postdexamethasone intact ACTH - but not to multisequential ACTH. Cortisol nonsuppressors showed higher postdexamethasone (only intact) ACTH values than Cortisol suppressors. Both postdexamethasone ACTH values were significantly and positively related with the postdexamethasone Cortisol values. We have established that Cortisol nonsuppression during melancholia is determined by an augmented escape of ACTH from suppression by dexamethasone. Intact ACTH showed the most significant clinical relevance for depression and Cortisol nonsuppression. In the clinical practice we advize the use of postdexamethasone intact ACTH in stead of plasma Cortisol or multisequential ACTH.