Neuropeptide Y (NPY) is widely distributed throughout the central nervous system and in several sympathetically innervated tissues, including the kidney. Although many central and peripheral acting endogenous compounds alter renal function, the role of NPY is unknown. Accordingly, we examined the effects of intracerebroventricular (ICV) or intrarenal administration of NPY on sodium and water excretion in the barbiturate anesthetized rat. Sprague-Dawley rats were uninephrectomized 10 days prior to testing and, in rats undergoing ICV administration, cannulae were implanted 3 days prior to testing. For testing, rats were anesthetized (Nembutal) and the jugular vein, renal artery and ureter catheterized. The results showed that the intrarenal infusion of NPY at 1 microgram/kg/min increased sodium and water excretion relative to the saline control group without altering blood pressure or creatinine clearance. Similarly, ICV administration of NPY at 10 micrograms in a 5 microliters volume increased the excretion of sodium and water without altering blood pressure as compared to the artificial CSF group. These findings suggest that both central and peripheral NPY may contribute to the regulation of sodium and water excretion in the rat.