The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. To determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. We measured lung clearance of inhaled 99mTc-DTPA aerosol in 20 normal non-smoking subjects before and after exposure to one hour's sidestream smoke inhalation. Measured carbon monoxide (CO) levels rose to maximum of 23.5 +/- 6.2 ppm (mean +/- SD) from baseline values of 0.6 +/- 1.3 (p < 0.001) and plasma cotinine levels to a maximum of 9.5 +/- 4.5 nmol/L (mean +/- SD). The half time (T1/2 in minutes) for 99mTc-DTPA clearance rose from baseline 69.1 +/- 15.6 (mean +/- SD) to 77.4 +/- 17.8 (p < 0.05) after smoke exposure. No effect of 99mTc-DTPA scanning or of sidestream smoke was demonstrated on lung function. We conclude that low level sidestream smoke inhalation decreases 99mTc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response.