To investigate the possibility of an autoimmune mechanism in idiopathic bilateral vestibulopathy (IBV), we screened patients' sera for antibodies against inner ear structures. IgG antibodies against membranous labyrinth (ampulla, semicircular canals, saccule and utricle) were detected in 8 of 12 patients by immunofluorescence on rat inner ear cryosections. All but one serum of 22 healthy controls and the sera of 6 patients with known autoimmune disorders showed only background staining. Low-titre anti-nuclear IgM antibodies were present in three control sera and one IBV serum. High-titre anti-nuclear IgM was found in a patient with lupus erythematosus and in one with scleroderma. Anti-nuclear IgM was not organ-specific. No human serum used contained detectable anti-vascular preformed antibodies. Cross-reactivity to sections of liver, kidney, cornea, brain and skeletal muscle was absent. Double-staining for IgG and F-actin, the primary constituent of hair cell cilia, did not show predominant Ig-coating of sensory hair cells. Immunosuppressive therapy in 3 IBV patients did not improve the disorder, probably owing to irreversible loss of sensory and neural structures. These data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, yet a small subgroup of organ-specific autoantibodies may synergize with a cellular response in the development of vestibular lesions.