We studied polymorphonuclear neutrophil (PMN) uptake in lungs of endotoxemic rabbits using 111In-labeled PMN and isotope imaging by gamma scintigraphy. Rabbits were challenged intravenously with 100 μg Escherichia coli endotoxin either 4 or 24 h before an intravenous injection of 111In- labeled PMN, which was obtained from donor rabbits. The contribution of CD18 glycoprotein (β2-integrin) on PMN was examined using an anti-CD18 monoclonal antibody (MAb) IB4 infused 20 min before 111In-labeled PMN injection. In control rabbits, 111In-labeled PMN uptake in lungs was maximal within 5 min [36 ± 2% increase above baseline (±SE)] and then fell exponentially with a disappearance half-time (t( 1/2 )) of 10 ± 2 min. In rabbits challenged with endotoxin for either 4 or 24 h, maximum 111In- labeled PMN lung uptake and t( 1/2 ) values increased to 52 ± 3 and 56 ± 3% and to 26 ± 2 and 31 ± 6 min, respectively. Pretreatment with MAb IB4 (0.5 mg/kg iv) did not alter the PMN uptake response and t( 1/2 ) values in the 4-h endotoxin-challenged rabbits (i.e., maximum uptake of 52 ± 3% above baseline and t( 1/2 ) of 26 ± 2 min), whereas MAb IB4 prevented the increases in lung PMN uptake and t( 1/2 ) in 24-h endotoxin-challenged rabbits (maximum PMN uptake of 26 ± 5% and t( 1/2 ) of 7 ± 3 min; P < 0.001). In contrast, the control MAb OKM-1 did not prevent lung PMN uptake and the disappearance of PMN from lungs at either times. These results indicate that endotoxemia stimulates an early CD18-independent PMN uptake in lungs and a late PMN uptake response mediated by CD18 integrin-dependent mechanisms.