Modern immunohistochemical methods allow a functional characterization of the human endolymphatic sac (ES) and its associated cell populations. The currently available immunohistochemical data on the extraosseous part of the human ES support the assumption that the epithelium is metabolically active and capable of both secretion and absorption. The reactivity of some epithelial cells with antibodies against neuroendocrine antigens implies a paracrine activity of the human ES. Further results provide evidence for a possible role of the human ES in inner ear immune defense and indicate a putative functional relationship of the human ES to the common mucosa-associated immune system.