We hypothesized that exposure of neonatal swine to chronic alveolar hypoxia (CH) would cause increased PVR, blunt acute hypoxic vasoconstriction, and increase VA/Q mismatch. After exposure to either normobaric alveolar hypoxia (FIO2 = 0.10) or room air for 2 weeks, animals were anesthetized and ventilated first with room air and then with hypoxic gas (FIO2 = 0.12). PVR, and pressure-flow (P/Q) relations were measured between 15-100% of baseline cardiac output. VA/Q matching was measured by the multiple inert gas elimination technique. During room air breathing, the mean PVR and P/Q slope in the CH animals was significantly greater than in the control (C) animals. P/Q intercepts were similar and near the origin for both groups. The absolute PVR and P/Q slope were greater for CH compared to C animals during acute alveolar hypoxia. The fractional increase in PVR and P/Q slope in the response to acute hypoxia was similar for both groups. PaO2, intrapulmonary shunt, and SDQp (an index of VA/Q heterogeneity) were similar for both groups. We conclude that CH in neonatal swine causes pulmonary hypertension, but does not attenuate acute hypoxic pulmonary vasoconstriction, nor VA/Q matching.