This study describes a high-frequency oscillatory ventilation (HFOV) protocol for term and near-term infants with acute respiratory failure (ARF) and reports results of its prospective application. Neonates, with gestational age >or= 34 weeks, were managed with HFOV, if required, on conventional ventilation (CV), a fraction of inspired oxygen (F IO(2)) 0.5, and a mean airway pressure > 10 cm H (2)O to maintain adequate oxygenation or a peak inspiratory pressure > 24 cm H (2)O to maintain tidal volume between 5 and 7 mL/kg of body weight. Seventy-seven infants (gestational age, 37 +/- 2,3 weeks), received HFOV after a mean duration of CV of 7.5 +/- 9.7 hours. Arterial blood gases, oxygenation index (OI), and alveolar-arterial difference in partial pressure of oxygen (P AO(2) - Pa O(2)) were recorded prospectively before and during HFOV. There were a rapid and sustained decreases in mean airway pressure (MAP), F IO(2), OI, and P AO(2) - Pa O(2) during HFOV ( P <or= 0.01). Seventy infants (91%) were weaned successfully from HFOV. Seven infants (P AO(2) - Pa O(2) prior to HFOV, 601 +/- 89 mm Hg) were classified as having experienced treatment failure and died from their underlying disease. Treatment failure was associated with lack of improvement in P AO(2) - Pa O(2) at 1 hour of HFOV ( P < 0.01). Early rescue intervention with HFOV is an effective protocol for term and near-term infants with ARF. Failure to improve P AO(2) - Pa O(2) rapidly on HFOV is associated with HFOV failure. Randomized controlled trials are needed to identify benefits of HFOV versus conventional modes of mechanical ventilation.