Abstract: Effects of serotonin (5-HT) on spontaneous discharges of single hypothalam ic arcuate neurons were observed in rat brain slices by extracellular recordin gs. The results showed that (1) of 149 neurons selected randomly and tested for 5-HT application, 33 (22.2%) were excited, 82 ( 55.0%) were inhibited, and 34 (22.8%) showed biphasic responses or failed to respond; (2) substitution of low Ca2+-high Mg2+ artificial cerebrospinal fluid (aCSF) for normal aCS F abolished the 5-HT-induced inhibitory effect but failed to affect the 5-HT-induced excitatory effect; (3) cyproheptadine, a non-selective 5-HT receptor antagonist, could block either the 5-HT-induced excitatory or inhibitory effects in all neurons tested; and (4) bicuculline, a GABAA -rece ptor antagonist, blocked the 5-HT-induced inhibitory effect. These result s imply (1) 5-HT excites arcuate neurons through a mechanism that is insen sitive to the decreased extracellular Ca2+, suggesting a direct postsynapt ic action of 5-HT on the 5-HT-receptors located in the membrane of th e neurons recorded; and (2) 5-HT might elicit the inhibitory effect through a Ca2+-sensitive release of GABA from intercalated GABAergic local neuro ns that are excited first by 5-HT.