Substance P (SP) is a polypeptide formed by 11 amino acids of the tachykinin family. SP is found in the peripheral nervous system, particularly in small diameter myelinated and non myelinated afferent fibers. It is concentrated at both proximal and distal ends of sensory neurones to the skin, mucous membranes, viscera and vessels throughout the body. In the central nervous system SP is concentrated in the basal ganglia (striatonigral system), the habenulo-interpeduncular system, the brain stem (particularly in afferent spinal tract neurones) and the hypothalamus. Neurones containing SP may also contain other neurotransmitters. Criteria for identification of SP are similar to those applying to other neuromediators except for duration of action, which is comparatively greatly prolonged for SP. SP exerts complex synaptic effects, both pre- and post-synaptic, and usually acts as an activating factor. Its physiological role is unknown but it could intervene in peripheral nociceptive processes by its peripheral (oedema and plasma extravasation) and central (excitation of dorsal horn sensory neurones and facilitation of medullary reflexes by depolarization of motor neurones) effects; in central regulation of nociceptive impulses (analgesic effect); in regulation of some vegetative functions (glandular secretion, digestive and vasomotor motility, hypothalamic functions); in certain motor regulatory actions as suggested by the large amounts of SP in the striatonigral tract and the motor effects induced by injection of SP into the substantia nigra; in control of some learning processes; in control of growth of some central nerve fibers during development.