We examined the effect of nicotine on pulmonary epithelial permeability in man. Nicotine was administered from a chewing gum base given over a seven-day period. An index of pulmonary permeability was derived from the rate of clearance from the lung into the blood of 99mTcDTPA (diethylenetriamine pentacetate). In five nonsmoking volunteers there was no change in permeability for the seven-day study period. This lack of effect of nicotine alone was in striking contrast to the increase in epithelial permeability observed in five nonsmoking subjects who took up cigarette smoking.