We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired Oz fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O-2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain similar to 1,500 small pieces of lung (similar to 1.7 cm(3)). The coefficient of variation of flow increased (P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When adjusted for the change in total flow to each lung, 90-95% of the variance in the hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung (P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.