We administered sodium nitroprusside (SNP) to ten patients with acute hypoxemic respiratory failure and associated pulmonary hypertension to examine the hypothesis that a reduction in the outflow pressure faced by the left (LV) and/or the right (RV) ventricle during ejection might be associated with an increase in cardiac index (Cl), hence an increase in systemic O 2 transport (O 2t). We measured pressures and flows invasively and the right and left ventricular ejection fractions by gated scintigraphy before and during an infusion of SNP titrated to a reduction of the mean blood pressure (BP) and/or the mean pulmonary artery pressure (PAP) of 10% to 15%. SNP infusion (mean dose, 1.02 ± 0.62 μg/kg/min) (mean ± SD) resulted in a decrease in all of the mean BP (Δ −18 ± 22 mm/Hg; P < .05), the mean PAP (Δ −4.2 ± 4.2 mm Hg: P < .05) the mean PVRI (Δ −110 ±97 d/s/cm −5/M 2; P < .01), and the mean SVRI (Δ −470 ± 565 d/s/cm −5/M 2; P < .02). However, SNP infusion was without effect on any of the mean LV or RV ejection fractions, end-diastolic filling pressures, end-diastolic volumes (preload), Cl, or systemic O 2t. At a dose resulting in a significant reduction in the mean outflow pressure faced by both the LV and the RV, an infusion of SNP was not associated with any substantial change of forward flow in patients with acute PAH complicating ARF.