Cigarette smoking is an important risk factor for pulmonary emphysema. In vitro experiments document cigarette smoke-induced inactivation of alpha 1-proteinase inhibitor, a protein which is thought to protect the lung interstitium against the deleterious action of neutrophil elastase. To assess the relevance of this in in vitro findings, we have measured the functional activity of alpha 1-proteinase inhibitor collected by bronchoalveolar lavage from twenty healthy volunteers (10 heavy smokers and 10 non-smokers). The total inhibitor concentration was measured by radial immunodiffusion. The active inhibitor concentration was determined by virtue of its elastase inhibitory capacity. We used pure and active site-titrated porcine pancreatic elastase and a kinetic assay with succinyl-trialanine-p-nitroanilide in order to get reliable and accurate results. In smokers and in non-smokers the percentage of functionally active alpha 1-proteinase inhibitor in bronchoalveolar lavage fluid is 54 +/- 12 and 38 +/- 14%, respectively. This difference is not significant. Serum alpha 1-proteinase inhibitor is 100% active in both groups. Our data disagree with previous reports suggesting the presence of fully active alpha 1-proteinase inhibitor in bronchoalveolar lavage fluid of non-smokers and of partially active inhibitor in the lavage fluid of smokers.