The effects of direct variation in static middle ear pressure were studied in the acute guinea pig. Pressure differences of from −500 to +500 mm of H2O were examined. Pure tones were delivered to the test ear in a closed system and the sound pressure levels monitored with a condenser microphone and probe tube situated 2 mm from the tympanic membrane. The cochlear microphonic was recorded from a round window electrode. Both the relative impedance change and cochlear microphonic were noted at various middle ear pressure levels. The animals were perfused with Prussian blue and cochleas stained with osmic acid and prepared for histopathological study. It was found that negative pressure causes greater changes on impedance and transmission than positive pressure. Increase in positive pressure was found to cause a monotonic increase in input impedance and decrease in transmission. For negative pressures, the effect was nonmonotonic. Observed changes in transmission with both positive and negative pressures could be accounted for only in part by changes in input impedance of the middle ear. Morphological findings showed some discrete dilation of the vessels on the malleus and the tympanic membrane.Subject Classification: [43]65.24, [43]65.40.