In this study we examined long-lasting effects mediated by intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) on two voltage dependent potassium conductances in CA1 pyramidal neurons, i.e. the transient current I(A) and the delayed rectifier, and on the inward rectifier I(Q), a mixed sodium/potassium current. All experiments were carried out in hippocampal slices with the in situ patch clamp technique, in the whole cell mode. Neurons recorded 30 min to 3 h after a brief application of 30 nM corticosterone to slices from adrenalectomized rats, thus saturating MRs and occupying most of the GRs, displayed a large I(Q)-conductance similar to neurons in slices from the sham-operated controls. By contrast, if only MRs or only GRs were activated, the I(Q)-conductance was significantly smaller than for the corticosterone-treated group of cells, indicating that simultaneous activation of both MRs and GRs is necessary to achieve a large I(Q)-conductance. If corticosterone was applied in the presence of a protein synthesis inhibitor, the I(Q) conductance was significantly smaller than in the absence of the inhibitor. Properties of the I(A) and the delayed rectifier were not affected by the various corticosteroid treatments. In conclusion, the data indicate that in particular the I(Q)-conductance is under a gene-mediated control of corticosteroid hormones. The I(Q)-conductance is relatively low when only MRs are activated, as occurs for the rat in the morning under rest, and high when both MRs and GRs are occupied, as occurs at the peak of the circadian cycle and after stress. This finding suggests that MR- and GR-mediated events act in synergism to control the I(Q), thus contributing to regulation of cellular excitability under physiologically relevant conditions.