In an attempt to further evaluate the role of neutrophil elastase (NE) in the development of emphysema, we examined the immunologic quantity of NE bound to alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF) supernatant from 36 community-based older volunteers. They were classified into three groups: 10 current smokers with low attenuation areas (LAAs) on the lung computed tomography (CT) scans who were considered to have subclinical emphysema, 13 current smokers who had a comparable smoking history but no LAA, and 13 noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was significantly increased in the subjects with subclinical emphysema when compared not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52 +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory activity measured by a spectrophotometric method using methoxysuccinyl-alanyl-alanyl-prolyl-valyl-paranitroanilide did not show any significant difference between the two groups of current smokers. There was no difference in the pattern or density of native and proteolysed alpha 1-PI bands between the three groups by Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that may differentiate smokers who are potentially developing emphysema from those who are not.