A number of laboratories have identified several key areas in the central nervous system that relay information from arterial baroreceptors to the supraoptic nucleus. Two of these regions are the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus. Recent findings suggest that the inhibition of vasopressin neurons in the SON by caval-atrial stretch may also involve the perinuclear zone. Using Fos immunocytochemistry in combination with volume expansion in unanesthetized rats, we observed that volume expansion activates a number of regions in the CNS including the area postrema, the nucleus of the solitary tract, the caudal ventrolateral medulla, the paraventricular nucleus, the perinuclear zone and oxytocin neurons in the supraoptic nucleus. Further experiments using pericardial catheters demonstrate that the activation of the nucleus of the solitary tract, the ventrolateral medulla, the paraventricular nucleus and the perinuclear zone by volume expansion is dependent on cardiac afferents. However, the Fos in the area postrema and oxytocin neurons of the supraoptic nucleus is not affected by removal of cardiac afferents. Similarly, electrophysiological experiments show that stimulation of cardiac receptors in the caval-atrial junction inhibits supraoptic vasopressin neurons but does not significantly affect the activity of supraoptic oxytocin neurons. These experiments suggest that while the inhibition of supraoptic vasopressin neurons during volume expansion is mediated by cardiac afferents, the activation of supraoptic oxytocin is independent of cardiac afferents and may be mediated by other visceral afferents or humoral factors. Additional electrophysiological experiments examined the importance of the perinuclear zone in cardiopulmonary regulation of vasopressin. Excitotoxin lesions of the perinuclear zone region block the inhibitory effects of caval-atrial stretch on supraoptic vasopressin neurons. This lesion has previously been shown to block the inhibitory effects of arterial baroreceptor stimulation on supraoptic vasopressin neurons. Thus, 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. Also while the inhibition of supraoptic vasopressin neurons during volume expansion is mediated by cardiac afferents, the activation of supraoptic oxytocin neurons is independent of cardiac afferents and may be mediated by other visceral afferents or hormonal factors.