Previous studies using high-resistance sharp electrodes demonstrated that corticosterone (CORT) reduced GABAergic synaptic inhibition in CA1 neurons of the rat hippocampus in vitro. In the present study we used whole-cell gigaseal recordings to investigate the possible role of cytosolic factors in the transduction mechanism underlying this action. The perturbation of the intracellular milieu that occurs under these recording conditions abolished the CORT-induced decrease in inhibitory postsynaptic conductance. CORT actually increased GABAA receptor-mediated conductances in about 50% of the neurons tested when the whole-cell recording mode was employed. As in the high-resistance microelectrode studies, CORT did not change the resting membrane potential, action potential amplitude or input resistance. The results suggest that the reduction of GABAergic synaptic inhibition in hippocampal CA1 pyramidal neurons induced by CORT critically depends on the presence of cytosolic factors, which wash out during whole-cell gigaseal recordings.