This study compares the effect of arginine-vasopressin and phenylephrine on renal sympathetic nerve activity, arterial pressure, and heart rate in vehicle- and intraventricular 6-hydroxydopamine-treated conscious rabbits. In addition, this study examines the involvement of forebrain structures on these variables. In vehicle-treated rabbits, compared to phenylephrine, vasopressin produces a greater decrease in renal sympathetic nerve activity and heart rate for a given increase in pressure. After administration of intraventricular 6-hydroxydopamine, the responses produced with vasopressin are similar to those produced with phenylephrine. Analysis of catecholamine content in the nucleus of the solitary tract, parabrachial nucleus, area postrema, and spinal cord indicates that the only regions of significant catecholamine depletion are in the nucleus of the solitary tract and the spinal cord. Transection at the mid-collicular level does not alter significantly the responses of vasopressin or phenylephrine on renal sympathetic nerve activity or heart rate. This indicates that forebrain structures are not involved in mediating the enhanced buffering effect produced with vasopressin.