The effect of a direct antigen challenge to the endolymphatic sac on vestibular function was investigated in guinea pigs. Following keyhole limpet hemocyanin (KLH) challenge to the sac in systemically presensitized guinea pigs, caloric responses were examined in 18 animals on days 1, 7, 14, 21, and 28. Caloric responses were significantly suppressed in 13 animals by day 7; of these, 5 animals had recovered by day 14 and 8 animals had not yet recovered by day 28. The behavior of spontaneous nystagmus was examined every hour in 10 animals at intervals of 3 to 56 hours after sac challenge. Irritative spontaneous nystagmus preceding paralytic nystagmus appeared in 5 animals, for which the mean onset was 14.6 +/- 3.1 hours and the mean duration was 4.4 +/- 6.5 hours. Paralytic spontaneous nystagmus appeared in all animals, for which the mean onset time was 23.3 +/- 12.3 hours. Neither direct KLH primary challenge of the sac nor phosphate-buffered saline injection to the sac caused significant changes in the vestibular function. These results suggest that an immune response of the sac induces a vestibular disorder and may produce an attack of vertigo similar to that of Meniere's disease.