This paper reviews the regulation of hypothalamic vasopressin and oxytocin neurosecretory cells in the neural response to plasma volume expansion. Many questions remain unanswered regarding how an increase in volume affects neurohypophysial hormone secretion, what receptors are important in mediating this response, and which neural pathways are responsible for conveying the signal from those receptors to the hypothalamus. Plasma volume expansion activates regions of the central nervous system associated with inhibition of vasopressin release, oxytocin secretion, and inhibition of sympathetic nerve activity. Cardiac receptors, not arterial baroreceptors, are primarily responsible for activation of the regions associated with regulation of vasopressin secretion and sympathetic outflow. Other stimuli that as yet are undefined account for activation of oxytocin-secreting neurons. Electrophysiology experiments have measured the inhibition of vasopressin-secreting magnocellular neurons in the supraoptic nucleus by select stimulation of cardiac receptors in the caval-atrial junction. Further experiments suggest that the perinuclear zone, a population of neurons surrounding the supraoptic nucleus, is a necessary part of the pathway by which caval-atrial stretch decreases the excitability of vasopressin neurons. The perinuclear zone is also a necessary synapse for arterial baroreceptor-mediated inhibition of vasopressin neurons. This suggests that the neural pathways that inhibit vasopressin release in response to an increase in blood pressure and an increase in blood volume may overlap at the perinuclear zone of the supraoptic nucleus. Finally, the integration of various neural pathways activated by multiple receptors to ultimately determine the activity of magnocellular neurons and vasopressin secretion is discussed.