The relation between the solute permeability of th alveolar epithelium, characterized as a pore radius, and lung inflation was studied in anesthetized dogs. Pore radius was calculated from measurements of the rate of efflux of several radiolabeled solutes of known molecular size from alveolar saline. Individual animals were studied at two or more separate inflation volumes. The pore radius during the first volume studied averaged 20 A in high-volume animals (mean inflation 82% of capacity) and 15 A at lower volume (mean inflation, 47% of capacity). The difference was significantly P < 0.05. Lungs inflated to total capacity showed free solute movement across the lung epithelium. Increasing inflation volume in an animal always produced a larger pore radius. Decreasing the inflation volume did not produce a smaller pore radius; it remained the same or became larger. Volume induced increases in lung epithelial solute permeability do not reverse immediately at lower volumes, suggesting this phenomenon represents lung injury.