OBJECTIVE We hypothesized that the magnitude of response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn would correlate with the degree of baseline hypoxemia. METHODS We performed a retrospective chart review of 15 consecutive newborn infants with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide as part of a pilot study. Oxygenation index was calculated for each patient at baseline and 0.5 and 24 hours after the start of therapy and findings were compared by repeated-measures analysis of variance. Correlation was determined between baseline oxygenation index and 24-hour change in oxygenation index. RESULTS Patients had a rapid and sustained decrease in oxygenation index (66.7 +/- 14.8 vs 26.3 +/- 5.0 vs 12.9 +/- 2.8, baseline vs 0.5 hour vs 24 hours; p < 0.001) during the study period, and the change in oxygenation index was highly correlated with baseline oxygenation index (r2 = 0.98). Two patients were placed on extracorporeal membrane oxygenation support before the 24-hour time point because of overwhelming sepsis and severe cardiac dysfunction. CONCLUSIONS In patients with severe persistent pulmonary hypertension of the newborn, we conclude that the clinical response to inhaled nitric oxide is most dramatic in those patients with the most severe hypoxemia.