The aim of this study was to evaluate the effect of inhaled nitric oxide (NO) in newborns with acute hypoxaemic respiratory failure and the impact of this NO therapy on survival and the need for extracorporeal membrane oxygenation (ECMO). A cohort of newborns with a gestational age of > or = 34 weeks and an oxygenation index (OI) > 25 were prospectively evaluated. Patients were given NO at an initial dose of 10 parts per million (ppm). Oxygenation parameters were evaluated prior and during NO inhalation. From January 1994 to December 1996, 20 infants were enrolled in the study. Based upon their outcome, patients were divided into two groups: survivors with no need for ECMO, group A (n=8) and survivors requiring ECMO or nonsurvivors, group B (n=12). All infants approached or met ECMO criteria before NO inhalation. Eight patients (40%) were successfully managed with NO and conventional treatment (group A). Newborns in this group showed a rapid and sustained improvement of systemic oxygenation during NO inhalation. Mean arterial oxygen tension (Pa,O2) increased significantly from 4.5 kPa (34 mmHg) (95% confidence interval (95% CI) 1.9-7.1 kPa (14.4-53.7 mmHg)) to 10.1 kPa (75.7 mmHg) (95% CI 6.5-13.6 kPa (49.1-1023 mmHg)) after 1 h and was 9.0 kPa (67.7 mmHg) (95% CI 7.1-11.0 kPa (53.1-82.4 mmHg)) at 24 h. Conversely, none of the oxygenation parameters improved in the 12 patients who ultimately required ECMO or died (group B). The results indicate that inhaled nitric oxide can improve systemic oxygenation in newborns with acute respiratory failure and may reduce the need for extracorporeal membrane oxygenation support in candidates. Lack of a rapid response to nitric oxide may be an early predictor of unfavourable short-term outcome, prompting a move towards alternative treatments.