Isolated lungs from high-altitude rats compared with those from low-altitude rats have blunted hypoxic pressor responses. Because calcium is essential for the hypoxic pressor response and has been shown to be altered in the pulmonary arterial smooth muscle during high-altitude exposure, we wondered whether altered calcium metabolism might account for the blunted response. We attempted to unmask differences between high- and low-altitude rat lungs by altering extracellular calcium. The addition of calcium to the blood perfusate augmented the hypoxic pressure response of high-altitude lungs and depressed that of low-altitude lungs. Calcium addition did not affect pressor responses to angiotensin II, but slowed vasodilation after both angiotensin injection and removal of the hypoxic stimulus. The maximal KCl-induced contraction was blunted in rings of main pulmonary artery from high-altitude rats, but augmented in their aortic rings. Submaximally constricted (40 mM KCl) pulmonary arteries from low- but not high-altitude rats further constricted with calcium addition. Aortic rings exhibited an inverse behavior. Thus, calcium addition augmented the blunted vasopressor response in high-altitude rats lungs, possibly by an effect on lung arteries. The aorta and main pulmonary artery differ in calcium handling.