Other than the potentially therapeutic bronchodilatory influences of marihuana, very little is known of its biologic effects on the lung. To evaluate this problem, alveolar macrophages were harvested from rats by bronchopulmonary lavage and incubated in vitro with Staphylococcus albus and marihuana smoke of standardized 2.2-percent tetrahydrocannabinol content in graded amounts. After three hours, control alveolar macrophages inactivated 78.0 +/- 5.0 percent of the staphylococcal challenge. There was a dose-dependent depression of alveolar macrophage bactericidal activity, with 66.7 +/- 7.1 percent, 23.7 +/- 7.0 percent, 20.5 +/- 7.0 percent, and 11.4 +/- 7.6 percent of the bacteria killed following exposures to 2 ml, 4 ml, 6 ml, or 8 ml of marihuana smoke, respectively. Differential filtration of marihuana smoke revealed that the alveolar macrophage cytotoxin was present in the gas phase of the smoke and was water-soluble. Studies on purified tetrahydrocannabinol and on tetrahydrocannoabinol-extracted marihuana revealed that the impairment in alveolar macrophage function was not related to the psychomimetic or bronchodilatory components of marihuana.