To explore mechanisms of hypoxemia after acute pulmonary embolism, we measured regional pulmonary blood flow and alveolar ventilation before and after embolization with 780-mu m beads in five anesthetized, mechanically ventilated pigs. Regional ventilation and perfusion were determined in similar to 2.0-cm(3) lung volumes by using 1-mu m-diameter aerosolized and 15-mu m-diameter injected fluorescent microspheres. Hypoxemia after embolization resulted from increased perfusion to regions with low ventilation-to-perfusion ratios. Embolization caused an increase in perfusion heterogeneity and a fall in the correlation between ventilation and perfusion. Correlation between regional ventilation pre- and postembolization was greater than correlation between regional perfusion pre- and postembolization. The majority of regional ventilation-to-perfusion ratio heterogeneity was attributable to changes in regional perfusion. Regional perfusion redistribution without compensatory changes in regional ventilation is responsible for hypoxemia after pulmonary vascular embolization in pigs.