Alterations in the physiological balance to maintain the pulmonary circulation at a normal low pressure level result in an elevation in pulmonary vascular tone. Pulmonary vasoconstrictor responses were analyzed under some experimental conditions, which included microembolism, administration of vasoactive agents, hypoxia, and monocrotaline-induced pulmonary hypertension. It is widely accepted that these responses are highly localized and complex. In the present study, excised canine lung lobes, rat lungs, and pulmonary arterial rings from the rat were employed according to the particular experimental design. The mechanism of the initial rapid elevation followed by a gradual decline in perfusion pressure in microembolism was considered to be related not only to the size of the emboli, but to the degree of mechanical injury of the endothelium. The main sites of constriction of the pulmonary vasculature by several drugs were determined in the pulsatile perfused canine lung lobes, according to the degree of decrease in inflow wave amplitude during antegrade or retrograde perfusion. Further, by applying the same method it was confirmed that the site of hypoxic vasoconstriction is located in the peripheral pulmonary vascular bed between the muscular arteries and veins, which are constricted mainly by serotonin and histamine, respectively. A cross perfusion system was set up, employing two lobes from the same dog, in which normoxic blood was perfused into the hypoxic ventilated lobe and vice versa. As a result, the pulmonary vessels showed a response to ventilation hypoxia that was far more sensitive than that to perfusion hypoxia. The effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol, pindolol) on hypoxic vasoconstriction were observed. Although pindolol (a vasodilatory beta-blocker) abolished hypoxic pulmonary vasoconstriction, which was similar to the effect of isoproterenol, the mechanism of action of pindolol was suggested to be different from that of isoproterenol. The importance of the K+ channel of vascular smooth muscle and also the endothelium in hypoxic pulmonary vasoconstriction were stressed. In isolated pulmonary artery segments of the monocrotaline-treated rat, the augmentation of sensitivity of the vascular smooth muscle to Ca2+ preceded the occurrence of pulmonary hypertension. Similarly, hyperreactivity to KCl and serotonin was also observed. It was clarified that the hyperreactivity induced by monocrotaline is modified by endothelium-dependent relaxation. Extensive cellular and molecular biological investigations are essential for further progress in this field.