The objective of this double-blind cross-over study was to evaluate montelukast for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two patients with EIB (post-exercise decrease in forced expiratory volume in 1 second (FEV1) ≥ 20% at pre-randomization) were randomized to montelukast 10 mg or placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary endpoint was the maximum percent-fall in FEV1 (from pre-exercise FEV1) during 60 minutes after exercise-challenge at 2 hours postdose. This endpoint was improved after montelukast (mean ± SD = 11.7% ± 10.8) versus placebo (17.5% ± 13.8) (p ≤ 0.001); numerically greater improvements were seen at 12 hours and 24 hours. A quicker time to recovery after challenge (p ≤ 0.001) and a smaller area under the curve for percent-fall in FEV1 during 60 minutes after challenge (p ≤ 0.01) were seen with montelukast at 2 hours. At this timepoint, more patients taking montelukast (45/54) than taking placebo (37/54) were protected against EIB (p = 0.039). We concluded that montelukast provided significant protection against EIB at 2 hours after a single dose. Copyright © 2007 Informa Healthcare.