Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral arteries and inhibits sympathetic tone in the heart in several mammalian species. We examined the possibility that a molecule related to porcine brain natriuretic peptide (pBNP), which acts at the same receptor sites as atrial natriuretic peptide, might provide an alternative source of natriuretic peptide to the cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse immunoreactive innervation of the heart, cerebrovascular tree, and renal arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the heart, innervating the atria most heavily and penetrating the ventricular myocardium along the coronary arteries. There was greater density of innervation of the right side of the heart compared with the left, particularly in the ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree was innervated by immunoreactive pBNP fibers, with the densest concentration of immunoreactive fibers along the surface of the internal carotid, middle cerebral, posterior communicating, and anterior cerebral arteries. The proximal renal arteries were not innervated, but as they approached the kidney, they were invested by bundles of immunoreactive pBNP fibers. These axons followed the major branches of the renal artery into the kidney parenchyma, running along the surface of the arterioles up to their entrance into the renal glomeruli. No immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian, or carotid arteries was seen. A substance related to pBNP may serve as a neuromodulator regulating cardiac output as well as blood flow in certain vascular beds.