Pulmonary clearance of technetium (99mTc)-labeled diethylene triamine pentaacetate (DTPA), a sensitive test of alveolar epithelial permeability, was measured twice in 34 healthy subjects, including 10 control nonsmokers (NS), 10 habitual smokers of marijuana alone (MS) (> or = 10 joints/wk), 9 regular smokers of tobacco alone (TS) (> or = 15 cigarettes/day) and 4 habitual smokers of both marijuana and tobacco (MTS). In smokers, the first study was performed after > or = 12 hrs of abstinence from smoking to assess chronic effects of marijuana and/or tobacco smoking on alveolar permeability; the second study was performed within 15 min of smoking to assess possible acute effects. TS exhibited abnormally rapid 99mTc-DTPA clearance after > or = 12 hours of abstinence, indicating an increase in pulmonary epithelial permeability, consistent with chronic tobacco-induced lung injury. MS showed a more modest and less consistent chronic effect than TS on 99mTc-DTPA clearance, suggesting a more variable and smaller degree of marijuana-induced lung injury. No acute effect of tobacco or marijuana smoking on 99mTc-DTPA clearance was apparent. Concomitant habitual smoking of marijuana and tobacco had no additive effect on alveolar permeability.