The canine pulmonary vascular bed has been studied with an in situ, blood perfusion system in the closed chest dog. Utilizing this system, the question as to whether or not the sympathetic nervous system modulates pulmonary vascular smooth muscle tone and blood flow was examined. Stimulation of the left stellate ganglion and administration of exogenous norepinephrine increased both intrapulmonary small artery and vein pressure. The responses of the pulmonary vasculature to both stimuli were abolished following the i.v. administration of phentolamine. In contrast, blockade of adrenergic neuronal transmission with guanethidine and bretylium, or destruction of the sympathetic nerves to the lung with 6-hydroxydopamine or 5-hydroxydopamine, selectively abolished the pulmonary vascular responses to stellate ganglion stimulation. Utilizing both electron microscopy and fluorescence microscopy of the adrenergic nerves, the data demonstrated noradrenergic innervation of the canine pulmonary arterial and venous vasculature. At least for the larger arteries, the density of adrenergic innervation appears to be present at the adventitial medial border of the veins and penetrates into the arterial media of the larger arteries. The data clearly indicate that when the adrenergic innervation is not destroyed by removal of the lung from the body, the canine sympathetic nervous system appears to regulate pulmonary vascular arterial and venous resistance and probably vascular compliance.