We hypothesized that the antibody -neutralization of L-selectin would decrease the pulmonary abnormalities characteristic of burn and smoke inhalation injury. In this study 3 groups of sheep (n=18) were prepared and randomized: LAM 1-3 group [1mg/kg of LAM 1-3 (mouse monoclonal antibody against L-selectin) was given intravenously 1h after the injury (n=6)], control group [no injury and no treatment (n=6)] and non-treatment group [injury, but no treatment] (n=6). All animals were mechanically ventilated during the 48h experimental period. P/F ratio (PaO₂/FiO₂) decreased in both LAM1-3 group and non-treatment group. Lung lymph flow and pulmonary microvascular permeability were both elevated following injury. This was significantly reduced when LAM1-3 was administered one hour after injury. Nitrate/nitrite (NOx) amounts in both plasma and lung lymph increased significantly after the combined injury. These changes were attenuated by post-treatment with LAM1-3. These results suggest that the changes in pulmonary transvascular fluid flux result from injury of lung endothelium by polymorphonuclear leukocytes. In conclusion, the post treatment with the antibody for the L-selectin improved the lung lymph flow and permeability index. L-selectin appears to be principally involved in the increased pulmonary transvascular fluid flux observed with burn/smoke insult. L-selectin may be a useful target in the treatment of acute lung injury following burn and smoke inhalation.