To determine the role of inhaled nitric oxide (NO) in a population of critically ill hypoxic near-term infants and to determine the dose response to inhaled NO, we examined a consecutive group of 23 infants referred for neonatal extracorporeal membrane oxygenation (ECMO) who had an oxygen index of 20 or greater after treatment with bovine surfactant. Inhaled NO was administered in concentrations from 5 to 80 ppm in random order to 23 infants. Overall, 13 infants had a significant response (an improvement in arterial oxygen pressure > 10 mm Hg or arterial oxygen saturation > 10%) to the first administration of inhaled NO, and one infant had a late response. There was no significant difference in the response to inhaled NO as measured by changes in arterial oxygen pressure or in the alveolar-arterial difference in partial pressure of oxygen, for any of the doses from 5 to 80 ppm. Thirteen infants had echocardiographic evidence of persisted pulmonary hypertension; 11 of these infants responded, compared with 3 responders among the 10 infants without persistent pulmonary hypertension of the newborn (p < 0.01). Overall, 11 infants required ECMO; there were two deaths in this group. Seven infants had congenital diaphragmatic hernia; five of those had a response to NO inhalation and four required ECMO. Our study demonstrates that there is no significant difference in response between low and high doses of inhaled NO and that this treatment may prevent the need for ECMO in some infants referred for this therapy, especially in infants with pulmonary hypertension. Prospective, controlled, randomized, and blinded trials of low doses of inhaled NO are needed to determine the clinical role of this potentially useful therapy.