We studied the airway gas exchange properties of five inert gases with different blood solubilities in the lungs of anesthetized sheep. Animals were ventilated through a bifurcated endobronchial tube to allow independent ventilation and collection of exhaled gases from each lung. An aortic pouch at the origin of the bronchial artery was created to control perfusion and enable infusion of a solution of inert gases into the bronchial circulation. Occlusion of the left pulmonary artery prevented pulmonary perfusion of that lung so that gas exchange occurred predominantly via the bronchial circulation. Excretion from the bronchial circulation (defined as the partial pressure of gas in exhaled gas divided by the partial pressure of gas in bronchial arterial blood) increased with increasing gas solubility (ranging from a mean of 4.2 x 10^-5 for SF₆ to 4.8 x 10^-2 for ether) and increasing bronchial blood flow. Excretion was inversely affected by molecular weight, demonstrating a dependence on diffusion. Excretions of the higher molecular weight gases, halothane (MW=194) and sulfur hexafluoride (MW=146), were depressed relative to excretion of the lower molecular weight gases ethane, cyclopropane and ether (MW=30, 42, 74, respectively). All results were consistent with previous studies of gas exchange in insolated in situ trachea.