Effects of the GABAB agonist baclofen on GABAergic transmission were examined before and after treatment with N-type (CgTX) and P-type (AGTX) Ca2+ channel blockers in cultured rat hippocampal neurons. Baclofen reduced GABAergic synaptic currents (IPSCs) without affecting the postsynaptic sensitivity to GABA. The presynaptic inhibition by baclofen was not blocked by Ba2+, a K+ channel blocker. IPSCs were reduced by treatment with either CgTX or AGTX, and completely abolished by treatment with both toxins. Both IPSCs after treatment with CgTX and those after AGTX treatment were similarly reduced by baclofen. The results indicate that both the transmission mediated by AGTX-sensitive Ca2+ channels and that by CgTX-sensitive Ca2+ channels are sensitive to baclofen, suggesting that activation of presynaptic GABAB receptors might inhibit both types of Ca2+ channels contributing to the GABAergic transmission in the hippocampus.