Inhaled nitric oxide (NO) and prone position (PP) are two of the new therapeutics proposed in the setting of acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the hemodynamic and respiratory effects of NO and prone position in patients with ARDS. Fourteen patients, sedated, paralyzed, and ventilated using volume-control mode, were prospectively investigated. All patients had a radial artery catheter, a pulmonary artery catheter, and a 3-F fiberoptic thermistor catheter advanced via the femoral artery into the descending aorta. The protocol consisted of seven phases: baseline measurements in supine position, SP (T0); SP + NO (T1); baseline 2 in SP (T2); PP without NO (T3); NO + PP (T4); SP + NO (T5); and PP + NO (T6). Inhaled NO (T1) induced an increase in PO2/FI(O2) (from 128 +/- 44 to 180 +/- 75 mm Hg, p < 0.004). Prone position (T3) resulted in an increase in PO2/FI(O2) (193 +/- 83 mm Hg, p < 0.003 versus T0). The association of NO with PP (T4) resulted in a significant improvement in PO2/FI(O2) (261 +/- 98 mm Hg) when compared with T0, T1, and T3. Analysis of variance showed a significant and additive effect of NO and PP on both PO2/FI(O2) (p < 0.000) and shunt fraction (QS/QT) (p < 0.01). Since the association of NO with PP presents additive effects on oxygenation, this association can be proposed for the treatment of ARDS.