Stress stimulates the secretion of the pro-opiomelanocortin (POMC) derived peptides ACTH and beta-endorphin (beta-END) as well as prolactin (PRL) from the adenohypophysis. The regulation of adenohypophysial hormone secretion is complex and includes a variety of neuropeptides and neuroamines. Histamine (HA) seems to participate as a neurotransmitter in the central regulation of adenohypophysial secretion and is involved in stress-induced release of these hormones. However, the effect of HA on POMC and PRL secretion is indirect and may involve activation of hypothalamic neurons subsequently releasing hypophysiotropic factors that in turn regulate adenohypophysial hormone secretion. In addition to the major hypothalamic factors regulating POMC and PRL secretion, corticotropin-releasing hormone and dopamine, the neurohypophysial peptides arginine-vasopressin (AVP) and oxytocin (OT) may serve such a regulatory role in adenohypophysial hormone secretion. We investigated this hypothesis at two different levels by a series of experiments presented in this review. The experiments aimed at studying: 1) the possible role of HA as a neuroendocrine regulator of AVP and OT secretion and neuronal activation, and 2) the possible involvement of AVP and OT in physiological regulation of POMC derived peptide and PRL secretion. In the first part of the study we found HA to be an important regulator of vasopressinergic and oxytocinergic neuronal activity and of AVP and OT secretion. The effect of HA is mediated via activation of both HA H1- and H2-receptors. The regulatory role of HA on the neuronal AVP and OT system is of physiological relevance since it is important for the adequate AVP and OT response to physiological stimuli such as dehydration and suckling. In the second part of the study we found that secretion of POMC derived peptides and PRL in response to stress and HA is transmitted via AVP but not via OT. The effect of AVP in HA- and stress-induced POMC and PRL secretion is both mediating and permissive and the AVP-receptors involved differ with respect to these two actions as well as with type of adenohypophysial hormone secreted.