In this study, we focused on the initial events of the injury response by studying mice four hours after the initiation of injury, which was induced by combining a very low dose of endotoxin with mechanical ventilation. The main finding was that a functional Fas/FasL system was required for neutrophil migration into the airspaces of the lungs of mechanically ventilated mice exposed to LPS. The changes in BAL neutrophils seen in this study were associated with changes in lung myeloperoxidase (MPO) activity, and because lung MPO activity is a measurement of the total content of neutrophils in the lungs, the data suggests that the Fas/FasL system is required for both neutrophil migration into the airspaces and for neutrophil recruitment into the lungs. This observation confirms other studies that suggest a key role for the Fas/FasL system in neutrophil migration into the airspaces; for example, activation of Fas in the lungs of mice and rabbits results in a neutrophilic alveolitis (1, 2) , whereas pharmacologic blockade of the Fas/FasL system attenuates the neutrophilic response to bacteria and bacterial products (3) (4) (5) (6) . Tissue respons. C57BL/6 or Fas-deficient lpr mice were exposed to either intratracheal installations of PBS followed by spontaneous breathing or to intratracheal installation of LPS, 15 ng/kg, followed by four hours of mechanical ventilation (MV) with tidal volumes of 10 mL per kilogram. Lung tissue sections were stained with hematoxylin and eosin to demonstrate the pattern of injury. The instillate contained 2.5% colloidal carbon to identify the instilled areas. Spontaneously breathing mice instilled with PBS showed normal lung architecture, regardless of strain (A, C). The B6 mice exposed to MV and LPS showed intra-alveolar and interstitial neutrophilic infiltrates, as well as thickening of the alveolar walls and occasional fibrin deposition (B).