The MRL-Fas^lpr mouse, a model of multisystemic autoimmune disease, has been proposed as a potential model of autoimmune inner ear disease. Cochlear pathology, consisting of hydropic degeneration of the stria vascularis, has been documented to occur coincident with the establishment of systemic disease in this animal. Because the cochlear pathology is restricted to the stria, this study was designed to evaluate whether the endocochlear potential (EP) would be diminished in these animals because of a loss in strial Na,K-ATPase. Experimental (MRL-Fas^lpr) mice, with established systemic disease, had auditory brain stem response thresholds and EPs recorded. MRL-+/+ mice served as controls. Animals were then euthanized, and their cochleas were processed for immunohistologic assay for the α1 and β2 subunits of Na,K-ATPase. Density of staining was evaluated by use of quantitative means with densitometry image analysis of digitized images. MRL-Fas^lpr mice revealed significant elevations in auditory brain stem response thresholds and reductions in EPs but no reductions in Na,K-ATPase levels, as evidenced by immunohitochemical assay. The reduction of EP likely occurs as a result of cellular degeneration within the stria vascularis and likely results from an abrogation of the strial perilymph/endolymph barrier and not from a reduction in strial Na,K-ATPase levels.