NPY a 36 amino acid peptide amide isolated from porcine brain, is a major regulatory neuropeptide in the mammalian central and peripheral nervous systems. NPY belongs to the pancreatic polypeptide family of peptides which are characterized by a common tertiary structure. Within this family, an intestinal peptide hormone, peptide YY (PYY), is most closely related to NPY. In the central nervous system (CNS) NPY is considered to be involved in regulation of blood pressure, memory processing, circadian rhythm, and stimulation of food intake. In the peripheral nervous system (PNS), NPY evokes potent vasoconstrictor activity and acts as a transmitter/neuromodulator of sympathetic neurons and adrenal glands. NPY is one of the most abundant peptides found in the CNS. NPY and NPY mRNA are widely distributed in the brain. High levels of NPY are present in the cerebral cortex, amygdaloid nuclei, hippocampal formation, and hypothalamus. In the PNS, NPY is widely distributed in sympathetic neurons that innervate vascular smooth muscle, heart, and urogenital tract. In these neurons NPY is mainly co-localized with norepinephrine and is considered to function as a neurotransmitter to presynaptically inhibit nor adrenergic neurotransmission. The biological actions of NPY in the brain and periphery are mediated by at least two different NPY receptors, designated Y1 and Y2 receptor subtypes. Cardiovascular effects and centrally evoked food intake potential are activities predominantly mediated by the Y1 receptors, whereas the Y2 receptors, the major subtype in the CNS, are mainly involved in the pre-synaptic inhibition of neurotransmitter release and facilitation of memory retention. Post-synaptic NPY receptors are apparently of both the Y1 and Y2 type. NPY receptors are coupled to at least two different signal transduction mechanisms, the adenylate cyclase pathway (decrease in cAMP), and the phosphoinositol/IP3 pathway. Antibodies that react specifically with NPY are useful for the study of the mode of action, differential tissue expression, and intracellular and subcellular localization of NPY in the central and peripheral nervous systems.