This study investigates the utility for depression research of an assay for intact (1–39) adrenocorticotropic hormone (ACTH) versus that of a previously employed (i.e., 1–17, 1–24 sequences) ACTH assay. ACTH plasma levels were measured using two different ACTH assays (labeled as intact versus nonintact) in 10 minor and 27 major depressed subjects undergoing the combined dexamethasone suppression (DST) and corticotropin-releasing hormone (CRH) test. Intact – but not nonintact – ACTH values were significantly correlated with the severity of illness. Major depressed subjects exhibited significantly higher post-DST+CRH intact ACTH values than minor depressives, whereas nonintact ACTH values were not significantly different between these groups. Post-DST+CRH intact ACTH values were significantly more closely related to post-DST+CRH cortisol than nonintact ACTH values. It is concluded that the assay of the intact ACTH molecule is an asset in depression research and should replace the previous less specific and sensitive ACTH assays.