Introduction: Exhaled breath nitric oxide (FeNO) is increased in asthma. NO is produced predominantly by inducible nitric oxide synthase (iNOS). We evaluated the selective and potent iNOS inhibitor GW274150 in asthma. Methods: 28 steroid naive asthma patients participated in a double-blind, randomised, doubledummy, placebo controlled, 3 period cross-over study. Subjects received GW274150 90mg, montelukast 10mg or placebo once daily for 14 days. FeNO was assessed pre-dose on days 1, 7, 10 and 14. AMP challenge was performed on day 10, allergen challenge on day 14 followed by methacholine challenge (MCh) 24hr later, then bronchoscopy. Results: GW274150 reduced pre-dose FeNO by 73%, 75% and 71% on days 7, 10 and 14 respectively compared with placebo. Montelukast did not reduce FeNO. GW274150 did not inhibit AMP reactivity while for montelukast there was a trend for inhibition; mean doubling dose (DD) difference vs placebo 0.64 (CI 0 to 1.28). GW274150 did not inhibit the early (EAR) and late (LAR) asthmatic responses to allergen, or MCh reactivity, despite reduced FeNO levels. Montelukast inhibited EAR and LAR FEV₁; mean difference vs placebo for minimum FEV₁ =0.37L (CI 0.19 to 0.55) and 0.18L CI 0.04 to 0.32)respectively. MCh reactivity was inhibited by montelukast (mean DD difference vs placebo 0.51; CI 0.02 to 1.01). GW271540 also had no effect on inflammatory cell numbers in bronchoalveolar lavage fluid post allergen challenge. Conclusion: Selective iNOS inhibition effectively reduces FeNO but does not affect airway hyperreactivity or airway inflammatory cell numbers post allergen challenge in asthmatics.