In the present study we report the effect of corticosterone in the regulation of hippocampal muscarinic acetylcholine receptor immunoreactivity (mAChR-ir) expression in rats. Adrenalectomy (ADX) or a single injection of a mineralocorticoid antagonist RU-28318 (1.0 mg/100 g body weight (b.w.)) in adrenally intact rats 24 h prior to sacrifice revealed an increased mAChR-ir in hippocampal CA1 and CA3 areas. Corticosterone replacement (100 microg/100 g b.w.) prevented the increase in mAChR-ir of ADX animals. However, glucocorticoid receptor antagonist (RU38486) treatment in adrenally intact rats failed to affect the mAChR immunolabeling. These results point to a modulation of muscarinic receptors by corticosterone that is predominantly mediated by the mineralocorticoid receptor.