Using an in vivo intracerebral microdialysis method coupled with an HPLC-fluorometric method, we investigated the extracellular level of endogenous histamine in the anterior hypothalamic area of urethane-anaesthetized rats. The basal rate of release of endogenous histamine in the anterior hypothalamic area measured by this method was 0.09 +/- 0.01 pmol/20 min. When the anterior hypothalamic area was depolarized by infusion of 100 mM K+ through the dialysis membrane or electrical stimulation at 200 mu A was applied through an electrode implanted into the ipsilateral tuberomammillary nucleus, histamine release increased to 175% and 188%, respectively, of the basal level. These increases were completely suppressed by removal of extracellular Ca2+. The basal release of histamine was also suppressed after infusion of 10(-6) M tetrodotoxin or i.p. administration of 100 mg/kg of alpha-fluoromethylhistidine. On the other hand, 3-fold increase in the basal release was observed after i.p. administration of 5 mg/kg thioperamide. These results clearly indicate that both the basal and evoked release of histamine measured by our method are of neuronal origin.