Kainate-type glutamate ionotropic receptors (KAR) mediate either depression or potentiation of inhibitory transmission. The mechanisms underlying the depressant effect of KAR agonists have been controversial. Under dual patch-clamp recording techniques in synaptically coupled pairs of CA1 interneurons and pyramidal neurons in hippocampal slices, micromolar concentrations of KAR agonists, kainic acid (KA, 10 µM) and ATPA (10 µM), induced inactivation of action potentials (APs) in 58% and 50% of presynaptic interneurons, respectively. Inactivation of interneuronal APs might have significantly contributed to KA-induced decreases in evoked inhibitory postsynaptic currents (eIPSCs) that are obtained by stimulating the stratum radiatum. With controlled interneuronal APs, KAR agonists induced a decrease in the potency (mean amplitude of successful events) and mean amplitude (including failures) of unitary inhibitory postsynaptic currents (uIPSCs) without significantly changing the success rate (P_s) at perisomatic high-P_s synapses. In contrast, KAR agonists induced a decrease in both the P_s and potency of uIPSCs at dendritic high-P_s synapses. KAR agonists induced an inhibition of GABA_A currents by activating postsynaptic KARs in pyramidal neurons, which was more prominent at dendrites than at soma. Both the exogenous GABA-induced current and the amplitude of miniature IPSCs (mIPSCs) were attenuated by KAR agonists. Thus, the postsynaptic KAR-mediated inhibition of GABA_A currents may contribute to the KAR agonist-induced decrease in the potency of uIPSCs and KA-induced disinhibition.