Although an autoimmune sensorieneural hearing loss has been considered as one of the inner ear diseases, the exact nature of responsible antigens are not clear because of the anatomical, developmental and physiological complexities of the inner ear. In this study, 32 guinea pigs were immunized with type II, IV, IX collagen, laminin and membraneous labyrinthine tissue. Audiometric and ultrastructural studies were performed on these animals to investigate the nature of the inner ear disease. The guinea pigs immunized with the combination of type II and IX collagens showed statistically significant hearing loss. However, the animals immunized with type IX collagen alone failed to show any change in hearing threshold. In ultrastructural study of the guinea pigs with severe hearing loss, irregular bleb at marginal layer of the stria vascularis and round shaped bulging at the inner pilla were seen. These results suggested the type II collagen could be a main responsible antigen to the inner ear lesion and type IX collagen could not contribute to induce the lesion.