A sensitive, rapid high-pressure liquid chromatographic assay was developed to compare the disposition of an intravenous dose of 14C-nicotine in normal, carefully matched smokers and nonsmokers. The elimination half-lifes of nicotine and cotinine were shorter in smokers than in nonsmokers. Also consistent with an inductive effect of smoking was the increased nicotine elimination rate constant in smokers, but smoking induced more complex kinetic changes: nicotine volume of distribution was diminished in smokers, whereas nicotine clearance and area under the concentration-time curve were unchanged. The presence of nicotine and its principal metabolites in a morning specimen of urine obtained from nonsmokers before 14C-nicotine administration suggests ubiquitous, passive exposure to and absorption of chemicals present in cigarette smoke.