Epithelial sodium channels (ENaC) are important for regulating sodium transport across epithelia. Functional studies indicate that neural mechanisms acting through mineralocorticoid receptors (MR) and sodium channels - presumably ENaC - are crucial to the development of sympathoexcitation and hypertension in experimental models of salt sensitive hypertension. However, expression and localization of the ENaC in cardiovascular regulatory centers of the brain have not yet been studied. RT-PCR and immunohistochemistry were performed to study ENaC and MR expression at the mRNA and protein levels respectively. Both mRNA and protein for , and ENaC subunits and MR were found to be expressed in the rat brain. All three ENaC subunits and MR were present in the supraoptic nucleus and magnocellular paraventricular nucleus, hippocampus, choroid plexus, ependyma and brain blood vessels suggesting the presence of multimeric channels and possible regulation by mineralocorticoids. In most cortical areas, thalamus, amygdala and suprachiasmatic nucleus notable expression of ENaC was undetectable, whereas ENaC and were abundantly expressed pointing to the possibility of heterogeneous populations of channels. The findings suggest that stoichiometrically different populations of ENaC may be present in both epithelial and neural components in the brain, which may contribute to regulation of CSF and interstitial [Na⁺] as well as neuronal excitation.