Histamine (HA) is synthesized from L-histidine by histidine decarboxylase (HDC), and HA released from neurons is predominantly methylated to tele-methylhistamine (t-MH), which is further metabolized by MAO. Therefore, the HA turnover rate is determined by either a exponential decrease in HA level after treatment with α-fluoromethylhistidine (α-FMH), a specific HDC inhibitor, or a linear accumulation of t-MH after pargyline treatment. Brain HA and t-MH can be simultaneously assayed using HPLC with fluorometric detection. Care should be given to avoid the contamination by extraencephalic mast-cell HA after microwave irradiation or immersion in liquid nitrogen, and to a marked circadian variation of t-MH level. The HA turnover is the highest in the hypothalamus, low in the pons-medulla oblongata and cerebellum, and nil in the spinal cord in rats, mice and guinea pigs. The half-life of neuronal HA is 8 ?? 87 min in various brain regions of these animals. Barbiturates, enflurane, benzodiazepines, GABA-mimetic drugs, ethanol and Δ9-tetrahydrocannabinol significantly decrease the HA turnover, whereas μ-opioid agonists such as morphine and [D-Ala2, McPhe4, Gly(ol)5] enkephalin enhance it. Footshock and phencyclidine also enhance it at least partly via μ-opioid receptors. Chlorpromazine, haloperidol, imipramine, methamphetamine or halothane have no influence on the HA turnover.