1. The aim of the study was to investigate whether inhaled leukotriene (LT) D 4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD 4 were compared with those of histamine and the mechanism of action sought. 2. Thirty-three non-atopic individuals participated in the study. The two drugs were inhaled as an aerosol of small particles causing a relative peripheral deposition pattern in order to mimic the preferential involvement of peripheral airways in asthmatic patients out of attack. 3. LTD 4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV 1 ) and peak expiratory flow rate. LTD 4 was 1900–7000 times more potent than histamine. LTD 4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. 4. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. 5. The reactivity of the airways did not change during 10 h after inhalation of LTD 4 as tested by repeated exercise challenges. 6. Pretreatment with ipratropium bromide prevented the effect of LTD 4 on FEV 1 , yet not on partial flow-volume curves. Pretreatment with either cimetidine and mepyramine or with indomethacin, did not affect the bronchial obstruction after LTD 4 . 7. In conclusion, peripheral deposition of LTD 4 in non-atopic subjects causes symptomless reduction in airflow with changes in lung function imitating that found in asthmatic patients out of attack. Unlike an allergen-induced asthmatic attack, inhalation of LTD 4 does not seem to induce bronchial hyper-reactivity to exercise nor a late reaction. These findings are compatible with LTD 4 as a mediator involved in bronchial asthma.