Previous maps of Type I corticosteroid receptor binding in the rat central nervous system (CNS) revealed a restricted distribution of the receptor in limbic regions, hypothalamus, and circumventricular organs. More recent studies have shown a more widespread expression of the receptor, with high levels of Type I receptor mRNA in limbic, motor, and sensory systems. We have used two antisera against peptide sequences derived from the cDNA of the human Type I corticosteroid receptor to map the regional distribution and corticosteroid regulation of the intracellular location of Type I corticosteroid receptor-like immunoreactivity (Type I-ir) in the rat CNS. Neurons showing Type I-ir were observed at all levels of the CNS. Highest densities of immunoreactive neurons were observed in limbic regions, isocortex, and some thalamic nuclei. Motor, sensory, and visceral systems often showed moderate densities of immunoreactive neurons. Type I-ir glia were observed in some fiber systems, e.g., corpus callosum, medial lemniscus, cerebral peduncles, spinal trigeminal tract, and funiculi of the spinal cord. In the majority of neurons and in glia, Type I-ir showed a diffusely nuclear and cytoplasmic location. Long-term adrenalectomy reduced immunoreactivity in most neurons and glia. Neuronal Type I-ir was localized mainly in the cytoplasm after long-term adrenalectomy. Nuclear immunoreactivity was retained in some neurons in the globus pallidus, motor trigeminal nucleus, and laminae 8 and 9 of the spinal cord. Acute treatment with corticosterone or aldosterone restored neuronal and glial Type I-ir to densities below that seen in intact rats.