Cigarette smoking alters the presence and function of alveolar macrophages. It has been speculated that these cigarette smoke-induced alterations contribute to the depressed pulmonary defense mechanisms commonly demonstrated in smokers. Studies of the phagocytic and bactericidal activities of alveolar macrophages from smokers and nonsmokers have yielded conflicting results. We tested whether alveolar macrophages from normal nonsmokers versus normal smokers differed in their ability to phagocytose and to kill the facultative intracellular bacterium Listeria monocytogenes. No significant differences in phagocytosis between nonsmokers and smokers were found. The alveolar macrophages from nonsmokers, however, killed Listeria, whereas those from smokers had no bactericidal or bacteriostatic activity. Thus, these data demonstrate that alveolar macrophages from normal smokers are able to phagocytose Listeria but express a selective functional deficiency in their ability to kill this facultative intracellular bacteria and, therefore, imply a defect in the immunoregulation of alveolar macrophages in smokers.