Macrolide antibiotics have immunomodulatory effects that may be beneficial to patients with chronic inflammatory pulmonary conditions. The aim of this study was to evaluate the effects of azithromycin on lung function, bronchial hyperresponsiveness (BHR), and airway inflammation in asthmatic children. Sixteen asthmatic children were treated with either azithromycin or placebo for 8 weeks. Lung function, BHR expressed as the dose-response slope (DRS) of forced expiratory volume in 1 second (FEV1) fall after hypertonic saline inhalation (DRS), and induced sputum were evaluated at baseline and after treatment. No significant change was observed in lung function before and after treatment. DRS (percent fall of FEV1/mL) decreased from (X +/- SD) 2.75 +/- 2.12 to 1.42 +/- 1.54 (p = 0.02) in azithromycin-treated children but not in the placebo group, which was 1.48 +/- 1.75 at baseline and 1.01 +/- 1.38 at the end of the study period. Neutrophil leukocytes decreased significantly in the azithromycin-treated group from 10 +/- 5.3% to 2.2 +/- 2.4% (p < 0.01) but not in the placebo group, with 7.2 +/- 4.2% at baseline and 3.3 +/- 3.6% at the end of the study. A short course of azithromycin is associated with amelioration of BHR and reduction in airway neutrophil infiltration in some children with asthma.