Rodent studies indicate that marijuana smoke can adversely affect the antimicrobial function of pulmonary alveolar macrophages (PAM). To evaluate whether marijuana smoke similarly affects human PAM, we compared phagocytosis, fungistatic/fungicidal activity, and superoxide anion (O2-) production of PAM recovered from marijuana smokers (MS), tobacco smokers (TS), marijuana and tobacco smokers (MTS), and nonsmokers (NS). Although PAM from the four groups were equally capable of ingesting Candida albicans, the macrophages from smokers differed from normal PAM in their ability to restrict intracellular yeast germination (ungerminated candida in smokers' PAM = 68 +/- 3% [46] versus NS = 54 +/- 6% [17], mean +/- SEM [n], p = 0.022). Despite heightened fungistatic activity, PAM from MS and TS destroyed significantly fewer intracellular yeast (28 +/- 2 and 29 +/- 2%, respectively) after 4 h than did macrophages recovered from NS (40 +/- 4%, p less than 0.05). Both basal and stimulated (dihydrocytochalasin B + opsonized zymosan or phorbol myristate acetate) O2- production were similar in PAM from MS and NS, but significantly increased in PAM from TS (p less than 0.05). Our findings indicate that marijuana smoking does not alter the phagocytic behavior or the respiratory burst of human PAM, but marijuana smoking does decrease the ability of human PAM to destroy ingested Candida albicans. These findings contrast with the effects of tobacco smoking, which not only decreases the fungicidal activity of human PAM but also increases their respiratory burst.