Secondary endolymphatic sac (ES) immune response against keyhole limpet hemocyanin (KLH) were immunohistochemically investigated in guinea pigs by analysing the distribution of IgG and C3 complement in the inner ear over a 4-week period. After systemic sensitization with KLH and Freund's adjuvant, KLH was inoculated into the right ES by trans-cranial approach. KLH was found in the ES immediately after KLH challenge and then disappeared on the 7th day. On the 2nd and 3rd day moderate endolymphatic hydrops and a massive cell infiltrations within the ES were observed, and they gradually decreased their severity with time. Diffuse stainings with IgG and C3 were found in the ES, the epithelial and subepithelial regions of the vestibule. Similar findings were obtained in the spiral ligament and the hair cells after antigen challenge. IgG bearing cells were detected within the endolymphatic sac alone. Our results suggested that endolymphatic hydrops may be produced by the imbalance of in-out flow of the endolymph and the immunologically mediated inflammation through IgG-complement system.