Hypoxic pulmonary vasoconstriction (HPV) is thought to protect gas exchange by decreasing perfusion to hypoxic regions. However, with global hypoxia, non-uniformity in HPV may cause over-perfusion to some regions, leading to high-altitude pulmonary edema. To quantify the spatial distribution of HPV and regional [Formula: see text] (P(R)O(2)) among small lung regions ( approximately 2.0cm(3)), five prone beagles ( approximately 8.3kg) were anesthetized and ventilated (PEEP approximately 2cm H(2)O) with an [Formula: see text] of 0.21, then 0.50, 0.18, 0.15, and 0.12 in random order. Regional blood perfusion (Q), ventilation (V(A)) and calculated P(R)O(2) were obtained using iv infusion of 15mum and inhalation of 1mum fluorescent microspheres. Lung pieces were clustered by their relative blood flow response to each [Formula: see text] . Clusters were shown to be spatially grouped within animals and across animals. Lung piece resistance increased as P(R)O(2) decreased to 60-70mmHg but dropped at P(R)O(2)'s<60mmHg. Regional ventilation changed little with hypoxia. HPV varied more in strength of response, rather than P(R)O(2) response threshold. In initially homogeneous V(A)/Q lungs, we conclude that HPV response is heterogeneous and spatially clustered.