Chronic cigarette smoking is an important risk factor for pulmonary and cardiovascular diseases. An increased production of cysteinyl leukotrienes has been shown in asthma and in cardiac ischaemia. The effect of cigarette smoking on cysteinyl leukotriene biosynthesis is, however, not known. Urinary leukotriene E4 (LTE4) was measured in 30 habitual smokers and in 30 non-smokers. In a further 12 non-smokers urinary LTE4 excretion was assessed before and after smoking six cigarettes. In addition, the effect of transdermal nicotine on urinary LTE4 excretion was studied in seven non-smokers. There was a close correlation (r = 0.92, P < 0.0001) between urinary excretion of LTE4 and the number of cigarettes smoked daily by habitual smokers. Smoking six cigarettes within 12h resulted in a significant (P = 0.0047), twofold increase in the mean individual LTE4 excretion in non-smokers. Transdermal nicotine had no effect on LTE4 excretion in non-smokers. In conclusion, cigarette smoke causes a dose-related increase in cysteinyl leukotriene production in habitual smokers. Some of the adverse effects of smoking may be related to an enhanced leukotriene synthesis.