When cigarette smokers with chronic lung disease stop smoking, they may do so with the aid of chewing nicotine gum. Smoking is known to accelerate the metabolism of theophylline, but the effects of nicotine gum on theophylline metabolism have not been determined. We studied the effects of nicotine and placebo gum on theophylline metabolism in healthy volunteers. Clearance of theophylline decreased by 32% after cessation of smoking in comparison to while chewing placebo gum. Clearance while chewing nicotine gum was similar to that measured while chewing placebo gum. Nicotine gum appears to have no effect on theophylline metabolism. For smokers who are chronically taking theophylline, the dose of theophylline will need to be reduced by one-fourth to one-third after smoking cessation and initiation of nicotine gum use.