Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons. The suppression of 5-HT responses was observed 1–4 hr after a brief (20-min) application of the steroids. Binding properties of the 5- HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABAB agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABAB and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine- induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.