Recent clinical experience and previous experimental work indicate that propranolol may reverse sodium-nitroprusside-induced inhibition of hypoxic pulmonary vasoconstriction (HPV). Accordingly, the authors decided to test this possibility in an experimental model that allows direct examination of pharmacologic influence on HPV. Six mongrel dogs were anesthetized with pentobarbital and intubated. Following a left thoracotomy, the left lower lobe (LLL) was ventilated independently but synchronously with the rest of the lung. Selective hypoxia of the LLL (95% nitrogen and 5% CO2) caused a 59 +/- 6% (mean +/- SE) decrease in the electromagnetically measured fraction of the cardiac output perfusing the LLL and a 287 +/- 65% increase in the pulmonary vascular resistance of the LLL from their respective prehypoxic values. Propranolol, 1 mg/kg intravenously, caused a 76 +/- 5% beta-blockade, as determined by an isoproterenol infusion test, but did not cause a significant change in the LLL HPV response. Sodium nitroprusside (SNP) infusion, caused a 38 +/- 4% decrease in systemic arterial pressure, and nearly abolished LLL HPV. Most important, the addition of propranolol to sodium nitroprusside did not significantly change the SNP induced inhibition of LLL HPV. The authors conclude that in acute lung disease, propranolol does not alter lobar HPV and does not reverse sodium nitroprusside inhibition of lobar HPV.