Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut. Infants with a suspected history of asthma were excluded. One hundred sixteen infants provided diary card data for the treatment period. Median age was 9 months. Infants on montelukast were free of any symptoms on 22% of the days and nights compared with 4% of the days and nights in infants on placebo (p = 0.015). Daytime cough was significantly reduced on active treatment (p = 0.04). Exacerbations were significantly delayed from montelukast compared with placebo (p < 0.05). In conclusion, cys-LT antagonist treatment reduces lung symptoms subsequent to RSV bronchiolitis.