Dopamine and isoproterenol, although used primarily for their inotropic effects, are also potent vasoactive substances. To determine their effects on the pulmonary circulation, we cannulated the left lower lobe bronchus in 20 dogs to permit ventilation with either air or a mixture of 95% nitrogen and 5% carbon dioxide; systemic oxygenation was maintained by venitlating the right lung with 95% oxygen. The lobe was perfused at a controlled flow rate and left atrial pressure was held constant. Hypoxic ventilation increased the lobar vascular resistance by 52% (p less than 0.001). Dopamine infusion (20 mcg. per kilogram per minute) during air ventilation also increased lobar vascular resistance by 50% (p less than 0.001). During hypoxic ventilation, dopamine increased the resistance by an additional 19% (p less than 0.001). In contrast, isoproterenol (0.2 mcg. per kilogram per minute) abolished the hypoxic pressor response (p less than 0.001). Combined alpha- and beta-adrenergic blockade did not alter hypoxia-induced vasoconstriction, whereas phentolamine blocked the dopamine response and propranolol abolished the isoproterenol-induced vasodilation. These results indicate the following: (1) The hypoxic pressor response is independent of sympathetic innervation; (2) dopamine in dogs is a pulmonary vasoconstrictor; and (3) isoproterenol is a pulmonary vasodilator. If these findings can be extrapolated to man, isoproterenol may be the preferred inotropic agent in patients with an elevated pulmonary vascular resistance.