Hindlimb ischemia and reperfusion lead to lung injury dependent on activated polymorphonuclear neutrophils (PMN) adherence. This study tests whether elastase and oxygen radicals participate in PMN-induced injury once they have become sequestered in lungs. Anesthetized rats treated with saline (n = 9) or the specific elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloromethylketone (MAAPV, n = 6) underwent 4 h of bilateral hindlimb tourniquet ischemia followed by 4 h of reperfusion. At this time, in saline-treated rats, PMN were sequestered in lungs as assayed by myeloperoxidase activity [(MPO) 51 +/- 5 U/g tissue], higher than MPO in saline-treated sham rats (n = 9; 18 +/- 3 U/g MPO; P less than 0.01); bronchoalveolar lavage (BAL) fluid leukotriene (LT) B4 levels increased to 594 +/- 46 relative to 200 +/- 38 pg/ml in shams (P less than 0.01); increased permeability was documented by BAL fluid protein content of 599 +/- 91 compared with 214 +/- 35 micrograms/ml in sham animals (P less than 0.01); and edema was shown by increase in lung wet-to-dry weight ratio of 4.77 +/- 0.14 relative to 4.00 +/- 0.09 in sham rats (P less than 0.01). In MAAPV-treated animals, lung neutrophil sequestration (62 +/- 9 U/g MPO) and rise of LTB4 in BAL fluid (780 +/- 244 pg/ml) were not affected, but both BAL fluid protein (335 +/- 32 micrograms/ml) and lung wet-to-dry weight ratio (4.21 +/- 0.17) were reduced (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)