In the rat brain, the hippocampus (HC) is a major target area for corticosterone (CT). In this study, we investigated the effects of CT in the in vitro slice preparation of the rat HC. Population spikes (PS) evoked by stratum radiatum stimulation were recorded in CA1. Bath-applied CT (10(-7)-10(-5) M) induced a decrease in the PS amplitude. This effect occurred within 10-15 min after the onset of CT perfusion, reached a plateau after 20-40 min and was reversible after 20 min washout. Neither dexamethasone (10(-5) M) nor vehicle produced any significant change in PS amplitude. Paired-pulse stimulation showed that the degree of inhibition of the second PS produced by the conditioning stimulus was either unchanged or decreased by CT. In the latter case, CT also reduced the inhibitory effect of gamma-aminobutyric acid on PS and enhanced the excitatory action of the opioid peptide D-Ala2-D-Leu5-enkephalin. These results show that CT reduces the excitability of HC pyramidal cells with a time course which may be compatible with a genomic action of CT. The fact that paired-pulse inhibition was either not changed or reduced, suggests that the decrease in PS size by CT is not due to an indirect excitatory effect of CT on inhibitory interneurons. Instead, CT may hyperpolarize pyramidal cells thus lowering their excitability and depressing the interneurons involved in recurrent inhibition.