To clarify the anatomical organization that allows for the synergy of vasopressin and oxytocin with corticotropin-releasing factor (CRF) in promoting adrenocorticotropic hormone secretion from the anterior pituitary, immunohistochemical double staining methods were used to compare the distribution of these peptides in the hypothalamic paraventricular nucleus of normal, colchicine-treated, and adrenalectomized male rats. In untreated animals, a few CRFstained cells were found in the parvocellular division of the paraventricular nucleus, while brightly stained oxytocin-and vasopressin-immunoreactive cells were centered in the magnocellular division. In animals treated with colchicine, an inhibitor of axonal transport, large numbers of CRF-stained cells were found in the parvocellular division of the nucleus, and 1-2% of these also stained with antivasopressin. As reported previously, a substantial number of oxytocin-stained cells, centered in a discrete anterior part of the magnocellular division, also expressed CRF immunoreactivity. In contrast, after adrenalectomy, CRF immunostaining of cells in the parvocellular division was enhanced selectively and >70% of these cells also stained positively for vasopressin. The distribution of oxytocin-stained cells was not influenced by adrenalectomy. The unusual localization of vasopressin immunoreactivity in parvocellular neurosecretory neurons in the adrenalectomized rat suggests that a single population of cells can produce CRF and vasopressin, both of which are potent promoters of adrenocorticotropic hormone secretion. These findings indicate that there is a state-dependent plasticity in the expression of biologically active peptides by individual neuroendocrine neurons.The isolation and characterization of a peptide that has potent corticotropin-releasing activity (1) has effectively ended a longstanding controversy as to whether the posterior pituitary hormone vasopressin might serve an additional role as the principal corticotropin-releasing factor (CRF) of the hypothalamus (2). Nevertheless, it is clear that both vasopressin and the related nonapeptide, oxytocin, can potentiate the effects of CRF on the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary (3-5). The anatomical organization of neurons that might allow for this kind of synergy is unclear.Physiological (6) and anatomical (7-10) studies indicate that neurons delivering CRF to hypophysial portal vessels in the median eminence are concentrated in a discrete zone of the parvocellular division of the paraventricular nucleus of the hypothalamus (PVH). In contrast, most oxytocinergic and vasopressinergic neurons in the PVH of the normal rat are concentrated in an anatomically distinct magnocellular division that projects to the posterior pituitary (11,12), though a few cells of each type are scattered throughout the The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 ...