Acute bacterial or viral infections responsible for pneumonia or sepsis cause severe inflammatory damage to the lungs, leading to the development of acute lung injury (ALI) in critically ill patients. ALI is characterized by high permeability pulmonary edema as well as refractory hypoxemia and diffuse pulmonary infiltrates. Our previous study has shown that the inducible NO synthase inhibition or the histamine H₁-receptor blockade significantly but incompletely inhibited LPS-induced lung vascular permeability in mice, suggesting that NO and histamine may also be partly responsible for mediating increased lung vascular leak following LPS challenge. The involvement of histamine in lung vascular leak has also been demonstrated using histidine decarboxylase gene knockout mice. Furthermore, treatment with the VEGF-neutralizing monoclonal antibody bevacizumab significantly reduced the LPS lung hyperpermeability response, suggesting active participation of VEGF in non-cardiogenic lung edema associated with LPS-induced ALI. We thus assume that several vascular permeability molecules, including NO, histamine, and VEGF, can be excessively produced and thereby actually contribute to the development of pulmonary edema in ALI.