This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction. A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline. Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids. Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.