The semicircular canal duct (SCCD) epithelium is a vestibular epithelial domain that was recently shown to actively contribute to endolymph homeostasis by Cl^- secretion under control of ₂-adrenergic stimulation. By analogy to other Cl^- secretory epithelia, we hypothesized that SCCD also provides an active absorptive pathway for Na⁺ under corticosteroid control. Measurements of short circuit current (I_sc) demonstrated stimulation (7-24 hrs) by the glucocorticoids hydrocortisone (EC₅₀: 13 nM), corticosterone (33 nM), prednisolone (70 nM) and dexamethasone (13 nM) over physiologically and therapeutically relevant concentrations and its block by amiloride (IC₅₀: 470 nM) and benzamil (57 nM), inhibitors of the epithelial sodium channel (ENaC). Isc was also partially inhibited by basolateral ouabain and Ba²⁺, indicating the participation of Na⁺,K⁺-ATPase and a K⁺ channel in Na⁺ transport. By contrast, aldosterone stimulated I_sc only at unphysiologically-high concentrations (EC₅₀: 102 nM). The action of all steroids was blocked by mifepristone (RU-486; K_d ~0.3 nM) but not by spironolactone (K_d ~0.7 µM). Expression of mRNA for the , and subunits of ENaC was demonstrated in the presence and absence of glucocorticoids. These findings are the first to identify SCCD in the vestibular labyrinth as a site of physiologically significant ENaC-mediated Na⁺ absorption and osmotically-coupled water flux. They further demonstrate regulation of Na⁺ transport by natural and therapeutic glucocorticoids. The results provide for the first time an understanding of the therapeutic benefit of glucocorticoids in the treatment of Meniere's disease, a condition that is associated with increased luminal fluid volume.