The powerful inhibition of CA3 pyramidal neurons evoked in rats (under urethane) by stimulating the fimbria or the perforant path from the entorhinal area is associated with a large increase in input conductance. Microiontophoretic applications of GABA produce a very similar large conductance increase, which is characterized by rapid fading, and causes a marked depression of the inhibitory postsynaptic potential (IPSP) conductance change. During repetitive stimulation at frequencies as low as 3–5/s, the IPSP conductance change can be much reduced, and it vanishes when electrical seizures begin. Since the effect of GABA is also reduced or abolished, a loss of efficacy of GABA (caused by desensitization or some other process) may be responsible for the failure of inhibition observed during tetanic stimulation, as well as for the subsequent seizures.