The effects of endotoxin (purified Escherichia coli lipopolysaccharide 0111:B4) on cochlear function in normal and otitis media animals were evaluated. Two types of experimental otitis media models were developed in guinea pigs: eustachian tube obstruction and intratympanic injection of endotoxin. In normal animals, three different concentrations (0.01, 0.1, or 1.0 mg/ml) of endotoxin were applied onto the round window membrane, and auditory brain stem responses were recorded at 1, 3, 6, and 12 hours and 1, 2, 3, and 14 days after the application of endotoxin. Concentrations of 0.01 and 0.1 mg/ml of endotoxin did not affect the auditory brain stem response thresholds, whereas a concentration of 1.0 mg/ml resulted in elevation of the auditory brain stem response thresholds. Alteration of the auditory brain stem response threshold began at 3 hours, reached a peak at 24 or 48 hours, and returned to a normal level 2 weeks after the application of endotoxin. However, when the same concentration (1.0 mg/ml) of endotoxin was applied to the round window membranes of animals that underwent eustachian tube obstruction or intratympanic injection of endotoxin, the endotoxin did not cause any alteration of the auditory brain stem response threshold compared with normal animals.