The hormone peptide tyrosine-tyrosine (PYY), first isolated from pig intestine, islocalized to endocrine cells in the lower bowel and exercises a predominantly inhibitory actionon gastro-intestinal function. Mammalian tissues also produce the homologous peptides neuropeptide Y, localized to central and peripheral neurons, and pancreatic polypeptide localized to thepancreatic islets. Analysis of tissue extracts from species of bird (chicken), reptile (alligator) and amphibian (frog) indicates that these classes of vertebrate also synthesize the three members of the peptide family that occur in mammals. Extracts of brain tissue from teleost (trout) and elasmobranch (dogfish) fish contain a neuropeptide Y-related peptide, but only a peptiderelated to PYY was identified in both pancreatic and gastrointestinal tissues. Only one member of the peptide family (peptide methionine-tyrosine), showing structural similarity to both neuropeptide Y and PYY, was found in brain and intestinal tissue of the Agnathan, Petromyzon marinus . The data suggest the hypothesis that an ancestral peptide gene underwent a duplication to produce a gene encoding neuropeptide Y and a gene encoding the common precursor of PYY and pancreatic polypeptide. A subsequent duplication of this latter gene gave rise to separate genes encoding PYY and pancreatic polypeptide. The primary structures of neuropeptide Y and PYY have been quite strongly conserved during vertebrate evolution whereas pancreatic polypeptide has undergone an accelerated rate of mutation.