Background: Anti-inflammatory properties of leukotriene modifiers and their effect on bronchial hyperresponsiveness have not been studied in children with asthma. Objective: The primary objective of this study was to determine the changes in serum levels of inflammatory mediators, clinical efficacy, and bronchial hyperresponsiveness after treatment with montelukast. Methods: In this double-blind, randomized, placebo-controlled trial, 39 children with mild-to-moderate atopic asthma were randomly allocated to receive montelukast or placebo for 6 weeks. Main outcome measures were changes in serum concentrations of soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1); peripheral blood eosinophil count; and eosinophilic cationic protein (ECP). Asthma severity score, FEV₁, and bronchial hyperreactivity (BHR) for histamine were secondary end points. Results: Compared to placebo, serum concentrations of IL-4, sICAM-1, and ECP and eosinophil blood counts significantly decreased after 6 weeks of treatment with montelukast. Montelukast significantly improved asthma control and FEV₁. Montelukast resulted in within-group significant decrease in levels of serum sIL-2R (611 vs 483 pg/mL), IL-4 (0.123 vs 0.102 pg/mL), sICAM-1 (280 vs 244 ng/mL), and ECP (74 vs 59 μg/mL) and in eosinophil blood counts (349 vs 310 cells/mm³). Mean FEV₁ value changed from 85% of predicted to 95% (P < .001) and for histamine (PC₂₀H) from 2.8 mg/mL to 3.8 mg/mL (P < .001) after treatment with montelukast. There was no significant difference between montelukast and placebo recipients in the serum concentrations of sIL-2R and PC₂₀H after treatment. Conclusion: Montelukast provides clinical benefit to patients with chronic asthma and decreases bronchial hyperresponsiveness. Montelukast caused a statistically significant decrease of serum concentrations in cytokine, ICAM-1, and ECP and peripheral blood eosinophil counts over the 6-week treatment period. This observation raises the possibility that leukotriene receptor antagonists, such as montelukast, may have effects on parameters of asthmatic inflammation. (J Allergy Clin Immunol 2002;109:257-63.)