In a canine model of acute respiratory failure, the authors investigated acute cardiopulmonary effects of nitroglycerin (TNG) and compared the results with those obtained after phlebotomy. Oleic acid increased intrapulmonary shunt (Qs/Qt) from 7.4 to 31% (P< 0.001) and decreased (P< 0.01) cardiac output (CO). In the presence of assumed low-pressure pulmonary edema, TNG was infused to decrease mean blood pressure (BP) by 40%; this was associated with a 26% decrease (P< 0.05) in CO. Qs/Qt increased from 31 to 42% (P< 0.01). There was a slight increase (P< 0.01) in pulmonary vascular resistance (PVR) with TNG, and mean pulmonary artery pressure (PAP) decreased (P< 0.05). In contrast, when CO was decreased by a similar amount with phlebotomy, mean Qs/Qt did not significantly change. There were similar changes in PVR and PAP and mixed venous O2tension with TNG and phlebotomy. Accordingly, current results rule out increased flow, increased Pvo2, and mechanical alterations in pulmonary vascular pressures as contributory to the increase in Qs/Qt with TNG. Alternatively, the increase in Qs/Qt with TNG may be explained by a direct pharmacologic decrease in pulmonary hypoxic vasoconstriction and/or by nonspecific pharmacologic effects.