Inhaled heparin has been shown to reduce the early and late phase of asthmatic reactions and suppress an allergen-induced increase in bronchial hyperreactivity. The mechanism involved in the control of bronchial hyperreactivity in asthma by heparin is still not understood. The purpose of this study was to investigate the effect of inhaled heparin on the airway response to histamine and leukotriene D4. Children with a typical history of mild allergic asthma participated in this randomized, double-blind, placebo-controlled cross-over study. Subjects underwent provocation challenge tests with histamine or leukotriene D4 before and after inhalation of heparin and placebo. Twenty-three patients completed the study. We showed that placebo did not affect the bronchial hyperreactivity to histamine or leukotriene. A single dose of inhaled heparin significantly decreased bronchial hyperreactivity to histamine and leukotriene in children with mild asthma. Results of our study suggest that inhaled heparin, because of its antiallergic and/or anti-inflammatory properties, modifies airway hyperresponsiveness in children with allergic asthma.