J. Clin. Invest. 109: 693–697 (2002). DOI: 10.1172/JCI200215218. activity of respiratory fluid is rather precarious, in that it can be abolished by altering the ionic milieu, by bacterial adaptation, and by as-yet uncharacterized abnormalities in nasal carriers of S. aureus. Studies of human airway epithelia maintained either in vitro or in nude mice demonstrate that respiratory epithelial cells generate antimicrobial activity even in the absence of glandular structures (5, 6). However, it has become clear that, compared with respiratory secretions collected in vivo, the antimicrobial activity of cultured airway epithelia is much less potent, perhaps because these cell culture models secrete a low-protein fluid that contains scant amounts of the major substances found in airway secretions (lysozyme, lactoferrin, SLPI, and defensins). In murine models, differentiation of airway epithelia into mucus-producing cells is dependent on Th2 cytokines IL-4,-5,-9, and-13, which may act predominantly through IL-9 (7). It remains to be shown whether the high-output production of antimicrobial proteins is also dependent on cytokineinduced differentiation of airway epithelial cells.