We studied the ultrastructural damage caused by venous air embolization in anesthetized sheep by morphological techniques after monitoring hemodynamics and lymph dynamics. Lung lymph flow and protein flux increased during 1 and 4 h of venous air embolization, results consistent with increased microvascular permeability. Histologically, the air emboli were restricted to the small pulmonary arterial vessels (1,000 to 100 micron in diam). Neutrophils accumulated around the air bubbles and formed intravascular clumps. Ultrastructurally, at the air embolus-blood interface, neutrophils appeared attached to a layer a proteinaceous material. Many neutrophils were in close contact with the pulmonary arterial endothelial cells. We found gaps (0.1-3 micron in width) between the endothelial cells of the pulmonary arterial microvessels. Beneath these gaps the basal lamina was disrupted. Other vessel types were unaffected. Some lymphocytes were seen near the air bubbles and the endothelial cell gaps. Platelets remained discoid, and fibrin clots were not observed. These results indicate that venous air embolization in sheep damages the pulmonary arterial microvessels. Neutrophils are closely associated to both the air emboli and the endothelial cell gaps.