Background: Montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. We and others have shown that there is a late-phase response 3 to 8 hours after exercise in a subset of asthmatic patients. Objective: We sought to evaluate the protective effect of montelukast on immediate-phase and late-phase responses after exercise challenges. Methods: Twenty-two atopic asthmatic children aged 7 to 16 years with reproducible exercise-induced bronchoconstriction (minimum of 15% decrease of FEV₁ from baseline) were enrolled in this placebo-controlled crossover study. Exercise challenges were performed while breathing cold dry air, and FEV₁ measurements were taken up to 480 minutes after exercise. Patients underwent exercise challenges on a screening day and 1 week after placebo treatment. Subsequently, after a week with no treatment, pulmonary function was assessed after breathing dry cold air (control day). Finally, an exercise challenge was carried out after a week of treatment with montelukast. Results: Reproducible late-phase reactions occurred in 5 of 22 patients, which correlated with the extent of the immediate response (P < .05). After 1 week of treatment with montelukast, a significant decrease of immediate responses was observed. Montelukast treatment compared with placebo was associated with a lower mean maximum decrease of FEV₁ (mean ± SEM: 17.3% ± 2.4% and 35.1% ± 2.6%, respectively), decrease of the area above the curve (267.8% ± 42.7%/min and 868.0% ± 103.8%/min, respectively), and shorter time for recovery (6.9 ± 1.1 minutes and 30.9 ± 4.0 minutes, respectively; P < .05). Treatment with montelukast also abolished late-phase responses. Conclusion: Once daily treatment with oral montelukast attenuated the immediate-phase response and abolished the late-phase response induced by means of exercise challenge in asthmatic children. (J Allergy Clin Immunol 2003;111:301-7.)