The presence and distribution of the transport protein complex Na+,K+-ATPase in the human endolymphatic sac (ES) was demonstrated immunohistochemically using a monoclonal antibody directed toward the denatured catalytic subunit of Na+,K+-ATPase from lamb kidney medulla. Our findings support an active transcellular ion exchange by the ES epithelium with subsequent passive transcellular and paracellular outflow of water. The possible role of the lateral intercellular spaces in the outflow of endolymph at the level of the ES is discussed.