Nitric oxide in exhaled air (FENO) is increased in asthmatic children, probably reflecting aspects of airway inflammation. We have studied the effect of the leukotriene receptor antagonist (LTRA) montelukast on FENO with a view to elucidate potential anti-inflammatory properties of LTRAs. Twenty-six asthmatic children 6 to 15 yr of age completed a double-blind crossover trial of 2 wk of treatment with 5 mg montelukast once daily versus placebo. FENO was measured during single-breath exhalation at a constant flow rate of 0.1 to 0.13 L/s against a resistance of 10 kPa/L/s. Eleven children were receiving maintenance treatment with inhaled steroids during the study (mean daily dose, 273 microgram), whereas the other 15 used only inhaled beta(2)-agonists as required. The within-subject coefficient of variation of FENO over a 2-wk interval for the 26 children was 38%. FENO was significantly reduced by 20% after the 2-wk treatment with montelukast as compared with placebo as well as compared with baseline. This effect occurred rapidly with a 15% fall in FENO within 2 d. The effect of montelukast on FENO was independent of concurrent steroid treatment. The effect on FENO is probably not caused by bronchodilatation since FENO increased significantly after inhalation of terbutaline. In conclusion, FENO in asthmatic children was significantly decreased from montelukast, which corroborates anti- inflammatory properties of LTRA.