These experiments show that a synaptic response, namely the late inhibitory postsynaptic potential (IPSP) of hippocampal CA3 neurons of rats, is blocked by pertussis toxin, an inactivator of several GTP-binding proteins (G-proteins) excluding the G-protein that stimulates adenylyl cyclase. This blockage occurred without a similar effect upon either the mossy fiber-evoked EPSP or the early (GABAa-mediated) IPSP. The toxin also blocked the response to baclofen, an agonist for a putative receptor (GABAb) mediating the late IPSP, but did not affect the response to THIP, an agonist for the receptor (GABAa) mediating the early IPSP. It is proposed that a pertussis toxin-sensitive G-protein controls the conductance of the late IPSP.