Heparin besides its anticoagulant properties, possesses anti-inflammatory actions. Inhaled heparin has been shown to reduce early and late phase of asthmatic reaction and suppresses allergen induced rise in bronchial hyperreactivity. The exact mechanism of heparin action in bronchial asthma remains obscure. The mechanism involved in the control of bronchial hyperreactivity by heparin has been studied little and is yet poorly understood. The purpose of the present study was to investigate the effect of inhaled heparin on the airway response to leukotriene D4 Fourteen children with typical history of mild atopic asthma participated in this randomized, double-blind, placebo controlled and cross-over study. At the first visit subjects underwent provocation challenge test with leukotriene D4. Patients came back 14 days later to inhale heparin or placebo followed by provocation test with leukotriene. The third study day was 14 days after the second day and provocation test was performed in the same manner except for that patients who inhaled heparin at the second visit, now were administered placebo and opposite. Ten patients completed the study. One patient was withdrawn from the study because of consent withdrawal and three patients were unable to complete the provocation test because of asthma exacerbation. Single dose of inhaled heparin significantly decreased bronchial hyperreactivity to leukotriene in children with mild asthma (p = 0.005). PC20L after heparin inhalation increased in eight patient and decreased in two. It has been shown that histamine, metacholine, and leukotriene play a role in eosinophil recruitment to the airway. Since histamine, metacholine and leukotriene act through receptor binding to protein G, it is possible that heparin (by displacing eosinophil proteins from receptor-protein G binding) restore binding between receptor and G protein and in such mechanism, decrease bronchial hyperreactivity to leukotriene. In our study heparin was inhaled just before leukotriene provocation test and thus the effect of heparin on eosinophil proteins is less likely possible.