Re-expansion of atelectatic lung is associated with increased permeability. This study tests whether neutrophils mediate this event. Right middle lobar atelectasis was induced in anesthetized rabbits (n = 18) by intraluminal obstruction of the bronchus after a 20-minute ventilation with 100% O2. After 1 hour of bronchial obstruction and 20 minutes after lobar re-expansion, leukopenia was noted, 2870 ± 210 white blood cells (WBC)/mm3, relative to control animals treated with a noninflated balloon catheter, 6500 ± 410 WBC/mm3 (p < 0.05). Three hours after re-expansion, neutrophils were sequestered in the previously atelectatic region 78 ± 7 polymorphonuclear leukocytes (PMN)/10 high-power field (HPF), as well as in nonatelectatic areas, 40 ± 3 PMN/10 HPF, higher than control values of 26 ± 3 PMN/10 HPF (p < 0.05). In the atelectatic region, neutrophil sequestration was associated with increased protein concentration in lobar bronchoalveolar lavage (BAL) of 1370 ± 100 μg/mL, higher than control values of 270 ± 20 μg/mL (p < 0.05). Re-expansion also induced increases in lung wet-to-dry weight ratio (W/d) of 6.2 ± 0.2, higher than control values of 4.3 ± 0.1 (p < 0.05). Rendering rabbits neutropenic (n = 18) (0 to 4 PMN/mm3) limited the atelectasis-induced protein accumulations in BAL (520 ± 60 μg/mL) and increase in lung W/d (5.2 ± 0.1) (both p < 0.05). Intravenous (I.V.; treatment of another group (n = 18) with an anti-CD 18 monoclonal antibody (R 15.7, 1 mg/kg) before balloon deflation prevented leukopenia (6550 ± 560 WBC/mm3), minimized neutrophil sequestration (36 ± 2 PMN/10 HPF), and attenuated protein leak (710 ± 95 μg/mL) and the increased lung W/d (5.6 ± 0.1) (all p < 0.05). A final atelectatic group (n = 9) was treated I.V. with the antiintercellular adhesion molecule-1 monoclonal antibody (RR 1/1, 1 mg/kg), which also prevented leukopenia and showed similar protection of microvascular barrier function. These data indicate that adherent neutrophils in large part mediate lung permeability and edema after atelectasis and re- expansion. Adhesion receptors of both neutrophils and endothelial cells regulate this event.