Acute middle ear (ME) and inner ear changes following brief unilateral phasic ME pressure changes (up to ± 6000/mm H2O) were studied in the guinea pig. Middle ear findings included perforation of the tympanic membrane, serous and serosanguinous exudate and hemorrhage of tympanic membrane and periosteal vessels. Changes were related to magnitude of applied pressure. Perforation and hemorrhage were more commonly seen with negative rather than positive pressure. Air bubbles behind the round window were seen with positive pressures. Occasional distortion, but never perforation of the round window, was noted. Hemorrhage of the scala tympani was observed with both positive and negative pressures; scala vestibuli hemorrhage was found with negative ME pressure. In some instances pressure direction and magnitude related changes were seen in the contralateral ear.