Oligodendrocyte precursor cells (OPCs) express receptors for many neurotransmitters, but the mechanisms responsible for their activation are poorly understood. We have found that quantal release of GABA from interneurons elicits GABA(A) receptor currents with rapid rise times in hippocampal OPCs. These currents did not exhibit properties of spillover transmission or release by transporters, and immunofluorescence and electron microscopy suggest that interneuronal terminals are in direct contact with OPCs, indicating that these GABA currents are generated at direct interneuron-OPC synapses. The reversal potential of OPC GABA(A) currents was -43 mV, and interneuronal firing was correlated with transient depolarizations induced by GABA(A) receptors; however, GABA application induced a transient inhibition of currents mediated by AMPA receptors in OPCs. These results indicate that OPCs are a direct target of interneuronal collaterals and that the GABA-induced Cl(-) flux generated by these events may influence oligodendrocyte development by regulating the efficacy of glutamatergic signaling in OPCs.