The activity of brain norepinephrine (NE) neurons in the locus coeruleus (LC) and peripheral sympathetic nerve activity (NE-SNA) in the splanchnic/renal nerve were recorded simultaneously during alterations of arterial blood pressure and circulating blood volume. Utilizing this experimental procedure we have previously found that both central and peripheral NE neurons are inhibited during blood pressure elevation. Furthermore, both neuronal systems were found to be inhibited during blood volume load, an effect apparently mediated by vagal afferents. In the present study both brain NE-LC activity and NE-SNA were increased during blood volume depletion. However, during prolonged hemorrhage the initial excitation of NE-SNA was followed by a marked inhibition. In contrast, the increase in NE-LC activity remained throughout the volume depletion period. The responses of central and peripheral NE neurons during hemorrhage were abolished in animals subjected to bilateral cervical vagotomy. Nitroprusside- or phenylephrine-induced blood pressure variations were associated with reciprocal changes in both central and peripheral NE neuronal activity. The NE-LC responses to blood pressure variations were abolished after bilateral vagotomy. NE-SNA responses, on the other hand, persisted after bilateral vagotomy. Our present and previous findings show that brain NE-LC neurons, similarly to peripheral NE neurons in the splanchnic/renal nerve, are regulated by tonically active cardiovascular afferents. Whereas peripheral NE-SNA is regulated by both arterial (high pressure) baroreceptors and cardiac volume (low pressure) receptors, the NE-LC neurons seem exclusively regulated by cardiac volume (low pressure) receptors.