The pulmonary vasculature responds to a multitude of constrictor and dilator mediators, but the exact physiologic and pathologic significance of such responsiveness is unknown. Further careful studies with specific mediator receptor blockers and synthesis inhibitors are required to determine if dilators play a role in maintaining the low vascular tone of the normal pulmonary circulation and if constrictors contribute to either the onset or the maintenance of the pulmonary hypertension associated with chronic airway hypoxia, lung injury, and pulmonary microembolism. It would be a mistake to summarily dismiss the possible involvement of vasoconstrictors in chronic pulmonary hypertension, but the apparent difficulty in establishing their importance emphasizes that mediators of vascular cell migration, proliferation, synthesis, and secretion may be at least as important in the etiology of the increased vascular resistance as the mediators of vascular tone.