AbstractWe compared intravenous and intratracheal administration of histamine (0.4 and 1.6 kg/kg, respectively) and nitroglycerin (5.0 and 20.0 μg/kg, respectively) in seven hypoxemic 2 week old lambs, during right lung only perfusion, to see if intratracheal administration could limit their vasodilator action to the pulmonary vessels. The hemodynamic variables: pulmonary artery pressure (Ppa), left atrial pressure (Pla), pulmonary blood flow per kilogram (Q/kg), and aortic pressure (Pao) were measured at baseline and in each experimental state, then pulmonary vascular resistance (PVR) and systemic vascular input resistance (SVR) were determined. We found that intravenous histamine showed some pulmonary vasodilator selectivity in that it caused a 19% decrease of Ppa from baseline (P < 0.002), a 23% decrease of PVR from baseline (P < 0.002). and an 8% decrease of SVR from baseline (P < 0.05). Intratracheal histamine produced smaller effects, decreasing Ppa by 11% from baseline (P < 0.02), and PVR by 14% from baseline (P < 0.02), while SVR was unaffected. Intravenous nitroglycerin decreased cardiac output by 16% from baseline (P < 0.02), and also decreased SVR by 8% while producing a small increase in PVR. Intratracheal nitroglycerin caused a similar 17% (P < 0.01) decrease in cardiac output, and again an increased PVR but a decreased SVR. This study confirms that histamine has some intrinsic pulmonary vasodilator selectivity. Furthermore, the data suggest that intratracheal administration may accentuate pulmonary selectivity by lessening systemic effects. Nitroglycerin, on the other hand, had untoward hemodynamic effects in the presence of hypoxia. © 1992 Wiley‐Liss, Inc.