We compared airway histopathologic findings in premature baboons given standard positive pressure ventilation with those seen after high-frequency oscillatory ventilation. Six animals received standard frequency conventional ventilation for a mean of 9.2 days; seven received high-frequency oscillatory ventilation at 10 Hz using a piston oscillator for a mean of 10.2 days; five baboons served as controls, and were killed immediately after birth. A semiquantitative histopathologic scoring system was used to grade tissue changes in the trachea, carina, and both mainstem bronchi. Compared with the nonventilated control animals, injury was produced with both forms of mechanical ventilation (P less than 0.01 for both instruments); however, the degree of damage was mild, with no significant difference in the extent of injury between the two treatment groups. High-frequency oscillatory ventilation appears to result in no greater degree of airway damage than conventional positive pressure ventilation.