This study demonstrates that degeneration of vestibular sensory cells depends on the integrity of immune responses in the endolymphatic sac (ES). Degeneration of the saccule occurred nearly twice as often as degeneration of the utricle and ampulla. Perilymph antibody levels were assessed following direct antigen (KLH) challenge to the endolymphatic sac in systemic presensitized guinea pigs. Mean perilymph antibody levels were significantly elevated in ears showing degeneration as compared to those which did not. Serum anti-KLH antibody levels were also significantly elevated in the ears with degeneration as compared to those without. Whether degeneration or recovery occurs, is largely dependent on the level of systemic immunization and perilymph antibody level within one week of antigen challenge to the ES.