Miniature spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABAA receptors were recorded using whole-cell patch clamp recordings in rat brain slices maintained in vitro at 34 +/- 1 degree C. We have found that firing of action potentials by principal neurons or by GABAergic interneurons is not necessary to the generation of sIPSCs since they persist in the presence of 1-5 microM tetrodotoxin (TTX). The average frequency of the discrete sIPSCs exhibits a large cell-to-cell variability and is between 5-15 Hz. The amplitudes of the sIPSCs depend on the difference between the membrane potential and the equilibrium potential for Cl- (ECl). Generally, 70-80 mV away from ECl, sIPSCs have a mean amplitude of 30-80 pA (i.e. peak conductance of 400-1000 pS) with an average decay time constant of 5.8 ms. Accordingly, unitary single sIPSCs arise from the simultaneous activation of no more than 20 GABAA receptor/channels. The perpetual barrage of spontaneous GABAergic activity is very likely to be a critical factor in the regulation of neuronal excitability and the mechanism of action of several neuroactive compounds.