In this study a possible role of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) in altering the access of corticosteroids to their receptors in the hippocampus is investigated. In vitro, oxidation of corticosterone to 11‐dehydrocorticosterone (11‐DHC) was demonstrated in hippocampal homogenates. Glycyrrhetinic acid (GE) and carbenoxolone (CBX) were potent inhibitors of 11β‐HSD activity and did not display affinity for mineralocorticoid (MRs) nor glucocorticoid receptors (GRs). Intracerebroventricular injection of CBX in vivo (ED₅₀∼30 μg) decreased oxidative activity in hippocampal homogenates, as demonstrated in vitro. In vitro, in hippocampal slices, cell nuclear retention of tritiated corticosterone, but not aldosterone, was markedly enhanced in the presence of GE, which at a concentration of 20 nM was found to inhibit 11β‐HSD activity by about 50% in the intact cell preparation. In contrast to the effect on in vitro cell nuclear uptake, in vivo autoradiography revealed that retention of corticosterone in the hippocampal cell nuclei was not affected after intracerebroventricular treatment with CBX.