Publisher Summary This chapter describes the pituitary regulation of adrenocorticotropin hormone (ACTH) and b-endorphin in endogenous depression. The advantages and difficulties are very well exemplified in the study of the hypothalamo-pituitary-adrenal (HPA) axis in endogenous depression. The design and interpretation of the endocrine studies in depression depends upon the understanding of pituitary regulatory strategies in normal and disease states. The chapter reviews the general feedback regulatory strategies at the pituitary level. The chapter presents the basic science studies on pituitary regulatory strategies in chronic stress animal models and pituitary regulation in diseases of the HPA axis with special emphasis on Cushing's disease, one of the best-characterized pituitary regulatory diseases. With this, it is easy to explore the question of pituitary regulation in endogenous depression. This chapter also focuses on the factors controlling the release of adrenocorticotropic hormone (ACTH) and related peptides. The delineation of the ACTH precursor, the isolation and sequencing of CRF, and the development of sensitive radioimmunoassays for ACTH and related peptides to replace less sensitive bioassay methods, have lent great impetus to the exploration of the HPA axis. These new tools enable a new level of sophistication in the studies of pituitary regulation in normal and disease states.