The cloning of the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) cDNAs provides a basis for understanding the actions of glucocorticoids in the central nervous system. Structural evidence is presented for the identity of the type I corticosteroid binding site as the MR expressed in the brain. This identification is supported by the anatomical distribution of MR mRNA, determined by in situ hybridization histochemistry, which parallels the steroid autoradiographic localization of the type I sites. An in vitro assay for MR and GR function demonstrates that these receptors respond to different levels of glucocorticoid, suggesting that together they confer a larger dynamic range of sensitivity to this hormone. These studies lead to a new hypothesis for glucocorticoid action in the central nervous system.