This chapter describes the synthesis of recent observations on synaptic and transmitter regulation of activity in neurohypophysial neurons on the basis of data mainly obtained in the rat supra-optic nucleus and emphasizes on vasopressin (VP)-synthesizing neurons and an elaboration of a portion of known inputs and associated transmitters regulating their excitability, particularly those of cardiovascular origin. The magnocellular neurons of the neurohypophysial system synthesize VP or oxytoxin (OXY) for release into the systemic circulation in the neurohypophysis. Oxytocin and vasopressin have been shown to influence the excitability of central neurons and to have a transmitter-like role, part of which is directed toward the magnocellular neurons themselves. Magnocellular neurons also contain several co-existing peptides, of which the opioid peptides have been most intensely studied. Opioid peptides are also present in afferent pathways to neurosecretory neurons and appear to have a predominantly depressant action on their excitability while other peptides located in pathways to magnocellular neurons include inhibin-related peptides and substance P.