Previous studies on the pressor response of the newborn pulmonary circulation to hypoxia have used intact animals and have reported conflicting results. Some have found an increase in responsiveness with increasing age; others have found a decrease. To circumvent many problems inherent in studies of pulmonary vascular reactivity in intact animals, we have developed methods for studying isolated, blood-perfused lungs from newborn rabbits. These methods have been used to study the influence of postnatal age on hypoxic pulmonary vasoconstriction. Two sets of experiments were performed. In the first, a stimulus response curve for hypoxic pulmonary vasoconstriction was constructed, using lungs from 19 rabbit pups that were 3–8 days old. At a constant blood flow, pulmonary artery pressure increased progressively as alveolar oxygen tension decreased so that the maximum increase from baseline (29.4 ± 4.7%) occurred at P1o2= 0. The pressor response to hypoxia was highly reproducible, and the entire system remained stable for over 2–3 hours. In the second set of experiments, we compared the pulmonary vascular response to hypoxia obtained using lungs from an additional 21 pups that were 3–8 days old with that obtained using lungs from 23 pups that were 10–14 days old. In response to the same hypoxic stimulus, pulmonary artery pressure increased more in lungs from older rabbit pups (56 ± 4%) than in lungs from younger rabbit pups (34 ± 7%) (p <0.001). We conclude that isolated perfused lungs from newborn rabbits exhibit a reproducible pressor response to alveolar hypoxia and that this response increases as a function of postnatal age.