The effect of alterations in the systemic oxygen tension on middle ear (ME) gas exchange was studied in three juvenile rhesus monkeys (Macaca mulatta) using five different inspired oxygen concentrations ranging from 15% to 100%. The anesthetized animals were ventilated for 4 hours, breathing the set of predetermined, constant oxygen-nitrogen gas mixtures. During this period, arterial and venous oxygen and carbon dioxide partial pressures were measured at 30-minute intervals; total ME gas pressure was determined indirectly using tympanometry at 10-minute intervals. Systemic oxygen blood gas tension showed predictable changes which were dependent on the fraction of inspired oxygen. However, fluctuations in the total ME gas pressure were insignificant. Findings suggested that increased systemic oxygen partial pressure does not influence ME gas exchange.