Regional cerebral blood flow is directly proportional to the Doppler velocity time integral of flow in corresponding cerebral arteries. This study was performed to determine whether an acute change in the velocity time integral of cerebral blood flow occurs in newborns with pulmonary hypertension who experience an acute improvement in pulmonary hemodynamics and gas exchange at the onset of inhaled nitric oxide therapy. Twenty-two newborns with lung disease and an oxygenation index >25 were treated with 10 to 20 parts per million inhaled nitric oxide. Measurements of heart rate, blood pressure, arterial blood gases, right and left ventricular planimetry, and Doppler ultrasonography were performed before and after 30 to 60 minutes of therapy. Nitric oxide inhalation was associated with a significant acute change in arterial blood pressure, pH, arterial carbon dioxide tension, arterial oxygen tension, proportion of right-to-left ductal shunt, estimated systolic pulmonary arterial pressure, and right ventricular diastolic and systolic areas. In the middle cerebral artery, peak systolic flow velocity (49+/-5 vs. 41+/-4, cm/sec), diastolic flow velocity (21+/-3 vs. 14+/-3, cm/sec), and the velocity time integral (10.3+/-1.1 vs. 7.9+/-1.1, cm) all decreased (p<0.05). These changes only occurred in a subgroup of 17 patients who experienced an improvement in arterial oxygen tension > or =10 mm Hg. The velocity time integral of flow in the middle cerebral artery is acutely decreased in newborns with pulmonary hypertension who experience an acute increase in oxygenation after the onset of inhaled nitric oxide.