Serotoninergic modulation of GABAergic mIPSCs was investigated in immature (postnatal 12-16-days old) rat CA3 pyramidal neurons using a conventional whole-cell patch clamp technique. Serotonin or 5-hydroxytryptamine (5-HT) (10 micromol/L) transiently and explosively increased mIPSC frequency with a small increase in the current amplitude. However, 5-HT did not affect the GABA-induced postsynaptic currents, indicating that 5-HT acts presynaptically to facilitate the probability of spontaneous GABA release. The 5-HT action on GABAergic mIPSC frequency was completely blocked by 100 nmol/L MDL72222, a selective 5-HT(3) receptor antagonist, and mimicked by mCPBG, a selective 5-HT(3) receptor agonist. The 5-HT action on GABAergic mIPSC frequency was completely occluded either in the presence of 200 mumol/L Cd2+ or in the Na+-free external solution, suggesting that the 5-HT(3) receptor-mediated facilitation of mIPSC frequency requires a Ca2+ influx passing through voltage-dependent Ca2+ channels from the extracellular space, and that presynaptic 5-HT(3) receptors are less permeable to Ca2+. The 5-HT action on mIPSC frequency in the absence or presence of extracellular Na+ gradually increased with postnatal development. Such a developmental change in the 5-HT(3) receptor-mediated facilitation of GABAergic transmission would play important roles in the regulation of excitability as well as development in CA3 pyramidal neurons.