Cholecystokinin octapeptide (CCK-8) occurs in relatively large amounts in some neurons of the cerebral cortex. Unlike most other mammalian neuropeptides, this compound contains a sulfate ester. We injected radiolabelled inorganic sulfate [( 35S]sulfate) into rat cerebral cortex and measured the formation and elimination of radiolabelled CCK-8 using HPLC. The data allow the first calculation of the turnover rate of a putative transmitter neuropeptide in brain. The turnover of CCK-8 (half-life = 16 h) is considerably slower than that of the biogenic amines and amino acid neurotransmitters (half-lives less than 4 h).