The role of the antiproteases at-proteinase inhibitor (e~PI) and mucus proteinase inhibitor (MPI) in human lung emphysema was investigated by measuring their amount and functional activity against trypsin, leukocyte elastase, and pancreatic elastase in the bronchoalveolar lavage fluid (BALF). In addition, leukocyte elastase was quantified in the lavage samples by measuring the concentration of the elastase-elPI-complex. The study population consisted of 38 patients (5 nonsmokers, 8 former smokers, 25 smokers) with aquired emphysema (i.e., emphysema which is not caused by elPI deficiency), and 44 individuals (16 nonsmokers, 8 former smokers, 20 smokers) without emphysema. No differences were found between patients with and without emphysema in the activities of cqPI and MPI, or in the concentration of exPI. The concentration of MPI was significantly higher in the BALF of patients with emphysema than in that of patients without emphysema (p = 0.025). A significantly higher concentration of elastase-cqPI complex was found in patients with emphysema than in those without emphysema (p = 0.041). This finding could reflect the higher proteinase burden to which patients with emphysema are exposed. The increase of MPI in lavage fluid of patients with emphysema seems to be the result of increased production in emphysematous lungs. However, it remains unclear why patients develop emphysema while showing an increased content of MPI.