To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (alpha-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (> 80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P < 0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in alpha-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients with ARDS, high levels of neutrophil elastolytic activity in the lungs are associated with reduced alpha-1-AP function.