Pulmonary alveolar macrophages lavaged from tobacco smokers release increased levels of oxidants and have been implicated in the pathophysiology of emphysema. It is unknown whether lung macrophages recovered from marijuana smokers also liberate excessive levels of oxidants. To evaluate this possibility, pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from nonsmokers, smokers of marijuana only, smokers of tobacco only, and smokers of tobacco plus marijuana. Spontaneous and stimulated superoxide anion release was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. These findings were correlated with recent lung function tests. Superoxide anion production by macrophages, studies of small airway integrity (closing volume, closing capacity, and the slope of Phase III of the single-breath nitrogen washout curve), and evaluation of alveolar gas exchange (diffusing capacity of carbon monoxide) were similar in both nonsmokers and marijuana smokers. However, tobacco smoking was associated with both significantly higher levels of superoxide anion release by pulmonary alveolar macrophages and significant abnormalities of small airway function and alveolar diffusing capacity. Based on the results of this study, pulmonary alveolar macrophages of marijuana-only smokers do not produce increased amounts of oxidants when compared to macrophages of non-smoking subjects. This observation may account for the absence of abnormalities in small airway function and alveolar diffusing capacity in marijuana-only smokers, in contrast to the presence of such findings in smokers of tobacco, regardless of marijuana use.