Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator which has proven effective in the management of pulmonary hypertension in children with congenital heart diease. It also improves oxygenation in acute hypoxemic respiratory failure (AHRF). In order to define the pharmaco- dynamics of iNO, a prospective, non randomized dose-response trial was conducted to examine the relationship between concentration of iNO and oxygenation in pediatric patients with AHRF. Mechanically ventilated children with AHRF were enrolled if the oxygenation index (OI) was ≥ 15 (OI=FiO2x100x mean airway pressure/PaO2). After recording baseline data, iNO was delivered continuously through the ventilator in sequential doses of 5, 20, 40, 60, and 80 parts per million (ppm) with a 20 minute equilibration period at each concentration prior to data collection. NO and NO2 concentrations were measured by electrochemical detectors placed in parallel. Response was defined as a 20% decrease in OI. Twenty dose-response trials were conducted in 19 patients, mean age 4.8 years (1 day - 18 years), with an entrance OI=36±21. Response criteria was met by 8/20 (40%) at 5 ppm and by 15/20(75%), overall, at a mean iNO concentration of 19±20 ppm. The maximum decrease in OI, 32±17%, occurred at 45±26 ppm iNO. At each dose of iNO the PaO2, the PaO2/FiO2 ratio, and OI were significantly improved compared with baseline (p<0.01). ANOVA (Dunett's post hoc test) indicated that OI, PaO2, and PaO2/FiO2 ratio improved with administration of 5 ppm iNO. Although OI continued to decrease with increases in iNO, in the group as a whole, these changes were not significant beyond 5 ppm. Thus, although individual patients recorded progressive improvement with increasing iNO dosage, the group as a whole displayed a plateau effect at 5 ppm. A similar plateau was observed when oxygenation was described by PaO2/FiO2 ratio. The ICU mortality of patients in the trial was 68% overall, 89% (8/9) for all oncology patients and 100% (6/6) for bone marrow transplant recipients.