Background: Cysteinyl-leukotrienes are increased in the airways of infants with virus-associated wheezing. We aimed to determine the effects of a cysteinyl-leukotriene-1 receptor antagonist on symptoms during an early-life wheezing illness and to investigate the factors that affect the response to this drug. Method: This placebo-controlled double-blinded randomized controlled trial recruited children aged 3-36 months with wheezing illness and randomized to active drug or placebo for 56 days. A symptom score diary (SSD) was kept by the children's caregivers. Results: One-hundred patients completed the study, and 62 (30 montelukast and 32 placebo) were analyzed. There were no significant differences in the percent of symptom-free days, symptom scores, and the need for rescue salbutamol between the two groups. However, the percent of symptom-free days within the first week was significantly higher for the montelukast than for the placebo group (13.8 +/- 4.1% vs. 5.4 +/- 3.4%; P = 0.028); wheezing score at 7th day was significantly lower for the montelukast than for the placebo group (0.5 +/- 0.1 vs. 1.4 +/- 0.2; P = 0.002). In addition, the number of inhaled ss 2-agonist rescue episodes per day during the first week was significantly lower for the montelukast compared with the placebo group (12.7 +/- 1.8 vs. 19.2 +/- 1.6; P = 0.013). Conclusions: Our results indicate that montelukast may be effective for reducing caregiver-observed wheezing and the need for salbutamol during the first week of treatment for early-life wheezing. The impact for caregivers and the optimal duration of treatment will need to be explored in studies of larger size.