In previous studies from this laboratory1 we have demonstrated that antibodies to ICAM-1 and CD11b significantly reduced endotoxin-induced airway inflammation but did not affect AHR. To further define the separate contributions of ICAM-1 and CD11b/CD18 to endotoxin-induced inflammation and AHR, we exposed ICAM-1-deficient mice, CD18-deficient mice, and background strain control (ie, wild-type) mice to an aerosol of endotoxin for 4 h. Endotoxin-exposed, CD18-deficient mice showed no changes in AHR or neutrophilic inflammation in the lung compared to endotoxin-exposed, wild-type mice. However, while endotoxin-exposed ICAM-1-deficient mice did not develop airway hyperreactivity, they mounted a normal inflammatory response to this toxin. The phenotypic differences that we observed in the ICAM-1-deficient mice and in the mice previously treated with ICAM-1 antibodies suggest that the IV administered ICAM-1 antibodies specifically prevent neutrophils from infiltrating the lung after endotoxin exposure but that reduced neutrophilic inflammation by itself has no effect on lipopolysaccharide endotoxin-induced AHR. Moreover, it appears that ICAM-1 is not required to facilitate the movement of neutrophils or polymorphonuclear leukocytes from the vascular space to the airspace, however, disruption of ICAM-1 prevents that development of lipopolysaccharide-induced AHR.