Established stereologic techniques were used to evaluate the morphologic integrity of isolated dog lungs perfused with plasma for periods of 30 minutes, 1 hour and 2 hours. The morphometric data from the isolated lung preparations were compared to similar morphometric evaluations of dog lungs fixed immediately after removal from the thorax. In the isolated lungs capillary surface and volume densities were both substantially decreased. These estimations of capillary surface density provide a morphologic definition of capillary surface area which should be useful in the estimations of endothelial permeability in isolated lungs. This morphometrically defined decrease in capillary volume density was attributed, in part, to swelling of the endothelial cells. Alveolar surface density was also decreased and the type-I epithelial cells were increased in thickness. In both the endothelial and epithelial cells, cytoplasmic volume densities of the mitochondria and smooth endoplasmic reticulum were increased, while those of the rough endoplasmic reticulum and micropinocytotic vesicles were unchanged. The thickness of the interstitial compartment of the air-blood barrier and the volume densities of the peribronchial, peribronchiolar, and perivascular connective tissue sleeves were unchanged; there was no evidence of interstitial edema in the isolated lungs. These morphologic change must be considered in the interpretation of physiologic studies which employ isolated perfused dog lung preparations.