• We compared the histologic alterations in the tracheae and bronchi of 30 premature baboons that were ventilated with either 100% or prn (as needed) oxygen (the fraction of inspired oxygen necessary to maintain the PaO2 between 50 and 80 mm Hg). The baboons were treated with either conventional positive-pressure ventilation (7 were treated with 100%; 7, prn) or high-frequency oscillatory ventilation (8 were treated with 100%; 8, prn). We used a semiquantitative scoring system to grade tissue changes in the trachea, carina, and main-stem bronchi. The fraction of inspired oxygen for all prn animals fell to a plateau of approximately 0.28 after 36 hours, where it remained for the duration of the study. The 15 100% baboons were ventilated for a mean of 139 hours, while the 15 prn baboons were ventilated for a mean of 151 hours. The findings in all conventional and oscillator-ventilated animals were similar and characterized by squamous metaplasia, cilia loss, and goblet cell loss. For both methods of ventilation, there were no differences in the injury scores between 100% and prn oxygen-treated animals. We concluded that there were no additional tracheobronchial histologic changes with 100% oxygen compared with prn oxygen.