Studies in whole animals, isolated lungs and pulmonary tissue strips have shown that the pulmonary vascular resistance (PVR) to hypoxia is temporally biphasic in nature. We studied the regional temporal response to hypoxia in prone pigs. The animals were ventilated with an [Formula: see text] of 0.21 (control), followed by an [Formula: see text] of 0.12 for 180min. A biphasic response in P(pa) to hypoxia was seen with the first peak between 10 and 20min and a second rise in P(pa) starting after 30min, which was due to an increase in cardiac output. Regional blood flow (Q ) and ventilation (V (A)) were measured using i.v. infusion of 15mum and inhalation of 1mum fluorescent microspheres, respectively. We grouped the lung pieces according to their temporal relative flow response to hypoxia. The five groups were each spatially distributed similarly, but not identically, among the animals. The corresponding relative ventilation to each group did not vary much. We conclude that in the prone pig, the PVR response to sustained hypoxia varies among regions of the lungs. Following an initial rise in PVR in most lung pieces, we found unexpectedly that some regions continue to increase PVR progressively and while other regions decrease PVR after the initial increase. The net effect is little change of overall PVR to hypoxia with time. Normoxic control animals had little change in their hemodynamics and the large majority of the lung pieces did not change their resistance over 3h. We speculate that the differential response of regions may be due to a differential role of nitric oxide, endothelin-1 release or K(+) channels.