We have presented our experience with the use of inhaled nitric oxide in children with congenital heart disease and pulmonary hypertension, which indicates that nitric oxide is a selective pulmonary vasodilator that may improve patient management, particularly after surgical procedures requiring cardiopulmonary bypass. Indeed, we have now seen several patients in whom all resuscitative maneuvers for the treatment of pulmonary hypertensive crises were unsuccessful until inhaled nitric oxide was added to the therapeutic regimen. In addition, our studies using inhaled nitric oxide as an investigational probe point toward endothelial injury as a contributor to post-cardiopulmonary bypass pulmonary vasoconstriction. Inhaled nitric oxide relieves pulmonary vasoconstriction associated both with left atrial or pulmonary venous hypertension and following the relief of mitral valve or pulmonary venous obstruction. Absence of a response on the usually reactive pulmonary vascular bed of the neonate should prompt a careful search for anatomic, and possibly surgically remediable, pulmonary vascular obstruction. In the short term nitric oxide is less effective in the older patient with obliterative pulmonary vascular disease. It is possible that recent experimental work with long-term nitric oxide inhalation might be applicable to this group of patients. Nitric oxide may have a unique role in the management of the patient after lung transplantation, as it both reduces right ventricular afterload and improves intrapulmonary shunting. Is nitric oxide the ideal agent for testing pulmonary vascular reactivity? Nitric oxide is simple to deliver by either mask or ventilator and, as a trial of vasoreactivity over 15 min, remains free of side effects that might be encountered during long-term administration, such as methemoglobinemia or nitrogen dioxide toxicity. Indeed, no patient developed significant methemoglobinemia after a trial of nitric oxide and neither was a level of nitrogen dioxide above 1 ppm registered during the administration. Thus, nitric oxide gas fulfills many of the ideal characteristics, as suggested by Rubin,92 required of a drug to test the acute responsiveness of the pulmonary circulation. It has better pulmonary dilating effects than systemic, a short half-life, and minimal adverse effects and it can be both easily and quickly administered. Whether it is able to reliably predict the effect of long-term administration of orally active agents awaits confirmation. Certainly, inhaled nitric oxide is rapidly becoming the standard agent to test pulmonary vascular reactivity during diagnostic cardiac catheterization at our institution.