The effects of serotonin (5-HT) receptor agonists and antagonists on the spontaneous discharge of suprachiasmatic nucleus (SCN) neurons were investigated using rat hypothalamic slice. It was found that: (1) the SCN neurons showed a persistent rhythm in the spontaneous discharge rate, which was higher during the light phase than during the dark phase; (2) the effects of 5-HT on SCN neurons was inhibitory in nature and the sensitivity of SCN neurons to 5-HT during the light phase was lower than that during the dark phase; (3) both 5-HT and 5-HT(1/7) receptor agonist, (+/-)-8-hydroxy-2-(DL-N-propylamino) tetralin hydrobromide, could inhibit the spontaneous discharge of SCN neurons. This inhibitory effect could be blocked by 5-HT(2/7) receptor antagonist ritanserin and putative 5-HT(7) receptor antagonists clozapine, but neither by selective 5-HT(2) receptor antagonist ketanserin, nor by 5-HT(1) receptor antagonist pindolol. It was suggested that the inhibitory effect of 5-HT on the spontaneous discharge of SCN neurons in rat hypothalamic slice is mediated by 5-HT(7) receptor subtype.