Caffeine metabolism is known to be accelerated in cigarette smokers, but the effects of smoking on the kinetics and pattern of metabolism in a daily consumption pattern have not been described. We investigated the effects of tobacco abstinence on the rate and pattern of caffeine metabolism in nine habitual smokers who consumed six cups of coffee per day, each cup containing 2 mg/kg caffeine. Abstinence from smoking for 4 days resulted in a 46% increase in the 24-hour AUC. Thus, significant, although probably not complete, normalization of the enzyme-inducing effects of cigarette smoking can be seen after 4 days abstinence. During abstinence, 24-hour urine ratios of dimethylxanthines to caffeine and mono-dimethylxanthines to dimethylxanthines were reduced, suggesting that cigarette smoking accelerates both demethylation steps. Other metabolic pathways were unaffected.