We have compared the macrophage elastolytic activity of a group of current and former smokers with irreversible airflow obstruction. Elastolytic activity was determined in an initial bronchoalveolar lavage cell population and in alveolar macrophages cultured for three days, to investigate whether enhanced macrophage elastolytic activity alone is a determining factor in the susceptibility of some smokers to obstructive lung disease. Twenty current smokers and 12 former smokers who had abstained from smoking for at least three years were studied. All patients had spirometric evidence of irreversible air flow obstruction. Current smokers had a cell yield (mean +/- SD) of 138.7 +/- 36.4 X 10(6) cells (alveolar macrophages 94.2% +/- 2.1%) compared with 31.4 +/- 14.1 X 10(6) cells (macrophages 86.5% +/- 4.7%) in former smokers. Elastolytic activity in the initial lavage cell population from current and former smokers, measured with the synthetic elastase substrate succinyl-L-alanyl-L alanyl-L-alanine-p-nitroanilide, and expressed as the equivalent of 1 microgram of porcine pancreatic elastase, was respectively 0.113 +/- 0.003 and 0.096 +/- 0.004 microgram pancreatic elastase/mg cell protein. After three days in culture macrophage elastolytic activity in the current and former smokers' cells was respectively 0.107 +/- 0.006 and 0.011 +/- 0.001 microgram pancreatic elastase/mg cell protein (p less than 0.05). The elastase activity of the cultured alveolar macrophages from five current smokers had the inhibitor profile of a metalloproteinase. Our results indicate that enhanced macrophage elastolytic activity alone is not a determining factor in the susceptibility of some smokers to develop obstructive lung disease.