The aim of this study was to investigate whether regular treatment with inhaled salmeterol modifies the dose-response curve to the inhaled short-acting beta2-agonist terbutaline or affects the concentration of nitric oxide (NO) in exhaled air of children with asthma. Twenty-two children aged 7 to 15 years (mean = 11.6 years) with mild asthma were treated with inhaled 50 microg salmeterol twice daily or placebo for 3 weeks in a randomized double-blind cross-over study. These treatments were followed by treatment with inhaled 200 microg budesonide twice daily for 3 weeks. On the last day of each period, NO level was measured in exhaled air and a cumulative dose-response experiment with terbutaline (cumulative dose: 1,475 microg) was performed. Baseline lung functions after salmeterol treatment were significantly higher than baseline after placebo (P + 0.05). Salmeterol treatment flattened out the dose-response curve to terbutaline such that higher doses of terbutaline were required to produce the same degree of bronchodilation (ED50 for FEV1 was increased by an estimated factor of 70 (95% CI: 0.8-6307) and ED50 for FEF25-75 by a factor of 41 (95% CI: 6.7-254); P < 0.05). NO levels were unaffected by salmeterol treatment (12.7 ppb; placebo = 10.7 ppb), but were significantly reduced during budesonide therapy (5.2 ppb; P < 0.001). The corresponding maximal NO levels were 19.5 (placebo), 22.9 (salmeterol), and 9.4 ppb (budesonide). We conclude that 3 weeks treatment with salmeterol does not affect NO levels in exhaled air, but it significantly changes the dose-response curve to terbutaline.