To determine the physiologic effects of inhaled nitric oxide (NO) on oxygenation and hemodynamics in children with severe hypoxemic respiratory failure, we studied the acute response to inhaled NO during mechanical ventilation in 17 pediatric patients. Diagnoses included adult respiratory distress syndrome (ARDS) (10 patients), bronchopulmonary dysplasia with viral pneumonitis (6 patients), and acute pneumonitis, caused by respiratory syncytial virus, without chronic lung disease (1 patient). Gas exchange and hemodynamic measurements were compared before and during exposure to inhaled NO (20 ppm) without changing ventilator settings for 30 minutes. Hemodynamic variables, including pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac index, were measured in 10 patients with ARDS. Inhaled NO acutely improved oxygenation in 15 of 17 patients; mean arterial oxygen tension increased from 58 +/- 13 mm Hg (baseline) to 86 +/- 25 mm Hg after 30 minutes (p < 0.01). Inhaled NO lowered mean pulmonary artery pressure (42 +/- 6 mm Hg at baseline to 31 +/- 6 mm Hg; p < 0.01) and intrapulmonary shunt (39% +/- 7% vs 32% +/- 7%; p < 0.01) without changing systemic arterial pressure or pulmonary capillary wedge pressure. Cardiac index increased by 14% (p < 0.01). Fifteen patients were subsequently treated with low-dose inhaled NO (3 to 10 ppm) for 1 to 24 days; 5 (50%) of 10 patients with ARDS and 7 (100%) of the 7 non-ARDS patients survived. We conclude that inhaled NO acutely improves oxygenation and lowers pulmonary vascular resistance without causing adverse hemodynamic effects in severe hypoxemic respiratory failure in pediatric patients. Inhaled NO may be a useful adjuvant therapy in children with acute hypoxemic respiratory failure, including infants with bronchopulmonary dysplasia, but whether prolonged low-dose inhalational NO therapy can reduce morbidity or improve survival rates remains unknown.