Established stereologic techniques were used to evaluate morphologic changes in isolated-perfused dog lungs after induction of severe, acute oncotic edema. Lung volumes occupied by the connective tissue spaces surrounding extraalveolar vessels and airways were increased. Thickness of the parenchymal interstitium (interstitial compartment of the air-blood barrier) was increased, creating an overall increase in mean thickness of the barrier. In the cellular compartments of the air-blood barrier, cytoplasmic volumes of the endothelial and type I epithelial cells occupied by pinocytotic vesicles were increased. The number of vesicles opening directly onto the luminal and abluminal cellular surfaces was increased. Transendothelial and transepithelial vesicular transport may contribute to edema formation in isolated perfused dog lungs. The production of oncotic edema was also associated with an increase in alveolar surface density; the proportion of the alveolar septa occupied by capillary contents was decreased.