This study was undertaken to elucidate the mechanism that causes sensorineural hearing loss in clinical cases with perilymphatic fistula. Perilymph was experimentally aspirated through the round window membrane in 17 guinea pigs. The extent of cochlear damage was examined electrophysiologically as well as histopathologically. Immediately after aspiration, several types of changes in summating potential (SP) were observed. Two animals without a polarity change of the SP showed only slight threshold changes in both cochlear microphonic and action potentials, and no specific histopathologic changes in the cochlea. Reversed polarity of the SP was observed in three animals, of which one showed a high-amplitude negative SP followed by rapidly progressive hearing loss. Bulging of Reissner's membrane was confirmed histopathologically in this case. The SP disappeared in the remaining 12 animals. In animals with profound electrophysiologic changes, bulging or rupture of Reissner's membrane and damaged hair cells were observed. These findings suggest that an abrupt change in perilymphatic pressure produces morphologic changes in the membranous labyrinth, causing changes in the vibration function of the cochlear partition and in the function of the organ of Corti. Abrupt pressure imbalance may be a causative factor of sensorineural hearing loss in the case of perilymphatic fistula.