Watson RR, Fu Z, West JB. Morphometry of the extremely thin pulmonary blood-gas barrier in the chicken lung. Am J Physiol Lung Cell Mol Physiol 292: L769-L777, 2007. First published November 17, 2006; doi:10.1152/ajplung.00355.2006.-The gas exchanging region in the avian lung, although proportionally smaller than that of the mammalian lung, efficiently manages respiration to meet the high energetic requirements of flapping flight. Gas exchange in the bird lung is enhanced, in part, by an extremely thin blood-gas barrier (BGB). We measured the arithmetic mean thickness of the different components (endothelium, interstitium, and epithelium) of the BGB in the domestic chicken lung and compared the results with three mammals. Morphometric analysis showed that the total BGB of the chicken lung was significantly thinner than that of the rabbit, dog, and horse (54, 66, and 70% thinner, respectively) and that all layers of the BGB were significantly thinner in the chicken compared with the mammals. The interstitial layer was strikingly thin in the chicken lung (ϳ86% thinner than the dog and horse, and 75% thinner than rabbit) which is a paradox because the strength of the BGB is believed to come from the interstitium. In addition, the thickness of the interstitium was remarkably uniform, unlike the mammalian interstitium. The uniformity of the interstitial layer in the chicken is attributable to a lack of the supportive type I collagen cable that is found in mammalian alveolar lungs. We propose that the surrounding air capillaries provide additional structural support for the pulmonary capillaries in the bird lung, thus allowing the barrier to be both very thin and extremely uniform. The net result is to improve gas exchanging efficiency. capillary stress failure; lung morphology; bird respiratory physiology; air capillary; extracellular matrix; interstitium IN THE VERTEBRATE LUNG, OPTIMAL thickness of the pulmonary blood-gas barrier (BGB) is affected by opposing selective pressures (65). The barrier thickness is minimized to allow efficient exchange of oxygen and carbon dioxide, yet the capillary walls must also be strong enough to withstand high pulmonary capillary pressures that are incurred during extreme physical exertion. The BGB is composed of three layers: capillary endothelium, an interstitial layer or extracellular matrix, and an epithelial layer (Fig. 1). Combined, these cellular layers are relatively thin, usually measuring Ͻ2 m in total thickness under normal conditions (5,33,36). This three-ply ultrastructure of the BGB appears to be evolutionally well conserved over a variety of vertebrate taxa, indicating that its basic structure is efficient and relatively immalleable (18,25,27,31,33). The strength of the pulmonary capillary walls is likely related to the morphometry of the BGB, where the thickness of the interstitium determines the fragility of the capillaries (5). Where the BGB is thinnest, the interstitial layer is composed of only the fused basement membranes of the endothelium and epithelium laye...