Airway epithelial cells not only constitute the physical barrier that separates airway lumen from interstitial compartments, but also actively participate in innate and adaptive immunity to protect the host from pulmonary infections [33] . Multiple defense systems have been evolved in airways. First, the polarized airway epithelia have a mechanical clearance mechanism. Goblet cells or submucosal glands secrete mucus that entraps airborne particles and inhaled infectious agents. Synchronized ciliary movement sweeps inhaled particulate matter toward the mouth to be expectorated or swallowed [34] #. Second, airway epithelia secrete antimicrobial factors, such as lysozyme and b-defensins [35] . Third, airways and alveoli are patrolled by phagocytic cells, most notably the alveolar macrophage, which can engulf microbes [36] . Fourth, airways can recruit neutrophils and monocytes to sites of inflammation [37] . Fifth, the acquired immune system, including antigen-stimulated T and B lymphocytes, provides cellular and humoral defenses for the airways [38, 39] . It is noteworthy that all the above-mentioned pulmonary defense mechanisms are executed in ASL, the thin film of liquid on top of the airway epithelia. Therefore, ASL homeostasis is pivotal to lung host defense. Here we provide the first evidence suggesting that ethanol exposure suppresses adenosine-stimulated chloride secretion that regulates ASL.