The alveolar epithelium is not injured by the apical application of moderate doses of Pseudomonas aeruginosa strains that produce protease. To determine the effect of Pseudomonas proteases on the basolateral surface of the alveolar epithelium, a series of experiments were done, in which P. aeruginosa strains that produce and do not produce proteases were administered intravenously. Subsequently, an innocuous dose of bacteria was instilled into the lungs of the rabbits. Although all the intravenous Pseudomonas strains increased the extravascular lung water to a similar degree, only the intravenous administration of the protease-producing P. aeruginosa strain increased the vulnerability of the alveolar epithelium to injury by the subsequent airspace bacteria. Bacteremia secondary to P. aeruginosa strains producing proteases could increase the chances of developing acute lung injury. Pittet, J. F., I. Kudoh, and J. P. Wiener-Kronish. 1998. Endothelial exposure to Pseudomonas aeruginosa proteases increases the vulnerability of the alveolar epithelium to a second injury. Am. J. Respir. Cell Mol. Biol. 18:129-135.