Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown to decrease pulmonary artery pressures but not increase cardiac output in hemodynamically stable patients with a variety of causes of pulmonary hypertension. The response to iNO in hemodynamically unstable patients with acute right heart syndrome has not been previously described. We determined the response to iNO in 26 critically ill adult patients with acute right heart failure defined by echocardiographic criteria. Patients received iNO through the inspiratory limb of the ventilator in increments of 10 ppm with hemodynamic and gas-exchange measurements made before and after each level. When maximal effect was seen, iNO was discontinued to compare parameters with baseline. iNO significantly increased cardiac output (5.5 +/- 3 to 6.4 +/- 4 L/min), stroke volume (54 +/- 27 to 65 +/- 38 ml), and mixed-venous oxygen saturation (69 +/- 8 to 73 +/- 10%), all p < 0.01. With discontinuation of iNO, all parameters returned immediately to baseline. These parameters of improved perfusion were related to a decrease in pulmonary vascular pressures and resistance. In a subset of approximately 50% of patients, these changes were substantial (> 20%) and in approximately 25% of all patients, the improvement in hemodynamic measures permitted a decrease in other vasoactive drug administration. The mean concentration of iNO required to achieve these effects was 35 ppm, and 85% of patients exhibiting a substantial improvement in hemodynamics did so at a concentration of iNO of less than or equal to 40 ppm. Underlying causes of right heart failure and baseline hemodynamics did not predict response to iNO, but the use of alpha-agonist catecholamines did. We conclude iNO improves hemodynamics in patients with respiratory failure, shock, and right ventricular dysfunction. Although mortality was not a key end point in this pilot study, it was high for both responders and nonresponders to this therapy. Further evaluation of the role of iNO in this patient population is supported by these data.