Objectives:To report a case of acute chest syndrome (ACS) of sickle cell disease treated successfully with nitric oxide and to review the physiologic effects of nitric oxide and its potential ability to improve outcome in ACS.Design:Descriptive case report.Setting:Eighteen-bed pediatric intensive care unit in a university children's hospital.Patient:A 15-yr-old black male with sickle cell disease, bilateral pulmonary infiltrates, refractory hypoxemia, and unstable hemodynamics.Intervention:In addition to exchange transfusion, invasive hemodynamic monitoring, and aggressive ventilatory support, inhaled nitric oxide was administered in the gas mixture in a concentration of 20 ppm for 72 hrs.Measurements and Main Results:Cardiac output, pulmonary arterial pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, shunt fraction, and alveolar-arterial oxygen gradient were compared with and without inhaled nitric oxide. Marked reductions in pulmonary arterial pressure and pulmonary vascular resistance were noted. Cardiac output improved, and shunt fraction and alveolar-arterial oxygen gradient were markedly reduced. The patient required decreased ventilator and hemodynamic support and rapidly made a complete recovery.Conclusions:Nitric oxide may be beneficial for patients with ACS because of its ability to ameliorate pulmonary hypertension and ventilation/perfusion mismatch. Nitric oxide may confer some protection against polymerization of sickle hemoglobin and exert a reversible antiplatelet effect that may be beneficial in ACS. Further study is necessary to determine the safety and efficacy of inhaled nitric oxide as a treatment for ACS.