AbstractThe neurokinins are a group of naturally occurring peptides with the common C‐terminal sequence Phe‐X‐Gly‐Leu‐Met · NH2. They include substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). SP and NKA are coded on the same gene, the PPT‐A, while NKB is coded on a separate gene, the PPT‐B. Neurokinins are present in the central nervous system and in peripheral organs where they exert various actions. They act on three receptors–NK‐1, NK‐2, and NK‐3–characterized through pharmacological, biochemical, and histochemical studies. Selective agonists for each neurokinin receptor were developed and evaluated on isolated smooth muscle preparations containing only one neurokinin receptor type. All three neurokinin receptors were cloned and expressed in Xenopus oocytes. Relative affinities of those receptors to neurokinins are the same as in their respective smooth muscle preparation. Finally, the mechanism of action of SP on histamine release from rat peritoneal mast cell has been studied and a direct activation of G proteins by peptides with basic amino acids is proposed as a working hypothesis.