Although immune-mediated inner ear disease was reported around 25 years ago, numerous attempts to identify the inner ear antigens have been performed. Experimental animal models have been used to study the immune mechanisms involved in hearing loss and to develop new therapies. Because animal models of autoimmune labyrinthitis have been developed by means of different antigens, we cannot yet show a valid immunopathologic explanation. A critical analysis of the more relevant experimental models employed has been performed in order to validate the methodology. Comparison between these models and animals with spontaneous systemic autoimmune disease has raised more questions concerning the pathophysiology of autoimmune hearing loss. A new pathogenetic theory is suggested, involving the supporting cells of the organ of Corti.