The ototoxic potential of bacterial endotoxin present in middle ear effusions was evaluated by inoculating endotoxin solutions of 10 micrograms/mL or 1000 micrograms/mL directly into the scala tympani of the guinea pig cochlea. Median auditory brainstem response threshold shifts of 12.5 and 20 dB were observed in the experimental ears exposed to the higher dose at days 2 and 4, respectively, with gradual improvement to near baseline by day 28. Histologic examination revealed inflammatory infiltrates in the scala tympani and scala vestibuli of several of these cochleas. The lower concentration, closer to that found in human effusions, elicited no significant loss of hearing and a milder inflammatory response. It is concluded that brief exposure of the cochlea to endotoxin from middle ear effusions is insufficient to cause hearing loss. Under chronic conditions, however, persistent inflammation within the cochlea may result in a sensorineural deficit.