Strenuous exercise combined with hypoxia is implicated in the development of high altitude pulmonary edema (HAPE), which is believed to result from rupture of pulmonary capillaries secondary to high vascular pressures. The relative importance of hypoxia and exercise in altering the distribution of pulmonary blood flow (PBF) is unknown. Six chronically catheterized SPF Yorkshire hybrid pigs (25.5±0.7 kg, means±SD) underwent incremental treadmill exercise tests in normoxia (F_IO₂ = 0.21) and hypoxia (F_IO₂ = 0.125, balanced order), consisting of 5 min at 30, 60, and 90% of the previously determined VO₂max. At steady state (~4 min) metabolic and cardiac output data were collected and fluorescent microspheres injected over ~ 30 s . Later the fluorescent intensity of each color in each 2 cm³ lung pieces was determined and regional perfusion calculated from the weigh-normalized fluorescence. Both hypoxia and exercise shifted PBF away from the ventral cranial lung regions toward the dorsal caudal regions of the lung, but hypoxia caused a greater dorsal caudal shift in PBF at rest than did near-maximal exercise in normoxia. The variance in PBF due to hypoxia, exercise, and vascular structure was 16±4.2%, 4.0±4.4% and 59.4±11.4%, respectively and the interaction between hypoxia and exercise represented 12±6.5%. This observation implies that there is already a maximal shift with in PBF with hypoxia in the dorsal-caudal regions in pigs that cannot be exceeded with the addition of exercise. However exercise greatly increases the pulmonary arterial pressures and therefore the risk of capillary rupture in high flow regions.