The effect of thyrotropin-releasing hormone (TRH), a neuropeptide physiologically present in the mammalian hippocampus, on spontaneous, miniature and evoked GABAergic postsynaptic currents was investigated using whole-cell patch-clamp recording from pyramidal cells and interneurons of the rat hippocampal thin slice preparation. Bath application of 10 μM TRH induced an increase in the frequency of spontaneous postsynaptic currents from 1.07 ± 0.68 to 3.16 ± 0.73 Hz in pyramidal neurons and interneurons of the stratum lacunosum-moleculare (SL-M). In tetrodotoxin solution TRH did not change miniature postsynaptic currents. Application of TRH to minislices containing only the CA1 region still produced an increase in the spontaneous postsynaptic current frequency, indicative of an action by TRH upon a local GABAergic circuitry. Paired recordings from one pyramidal cell and one stratum lacunosum moleculare interneuron displayed synchronous events whose frequency rose after TRH application, suggestive of a common, TRH-sensitive input. In a small subset of cells TRH induced the appearance of highly rhythmic large postsynaptic currents at a frequency of ∼2 Hz, as confirmed by autocorrelation analysis. Postsynaptic currents electrically evoked by focal stimulation of stratum lacunosum-moleculare were depressed from 90 ± 27 to 44 ± 15 pA after application of TRH. This phenomenon was solely due to an increase in the number of synaptic failures. It is proposed that the effect of TRH on the GABAergic system was primarily exerted on a subset of interneurons controlling the activity of pyramidal cells as well as stratum lacunosum-moleculare interneurons.