Ibuprofen is a cyclo-oxygenase inhibitor that is alleged to have additional direct effects on leukocyte function. These properties suggest that Ibuprofen may be of potential therapeutic value for neutrophil (PMN)-mediated acute lung injury in humans such as that resulting from septicemia by gram-negative organisms. This study quantitated the effect of pretreatment with Ibuprofen on the intensity of acute neutrophilic alveolitis following endotoxemia. The effect of Ibuprofen on neutrophilic alveolitis was biphasic: There was suppression of inflammation at a high dose (30 mg/kg), enhancement at a low dose (3 mg/kg), and intermediate doses (10–20 mg/kg) had no effect. In contrast, both 10 and 30 mg/kg of Ibuprofen prevented early hypoxemia following endotoxemia, suggesting that early hypoxemia and inflammation by neutrophils were not causally related. The dose of Ibuprofen required to suppress neutrophil alveolitis exceeds that required to inhibit cyclo-oxygenase in the model. Therefore, suppression of alveolitis by 30 mg/kg of Ibuprofen may depend on other pharmacologic properties of Ibuprofen such as its direct effect on neutrophil migration.