Extracellular purines are involved in allergen induced airway inflammation and regulation of Cl^- secretion by the airway epithelium. To study the role of extracellular purines in inflamed airways, mice were sensitised and challenged with ovalbumin (OVA). 24 and 72h after OVA challenge of BALB/c mice infiltration by eosinophils and increased airway responsiveness to methacholine was found. This was not observed in ecto-5´-nucleotidase (CD73) deficient mice (CD73 -/-). In tracheas of BALBc mice purine induced Cl^- secretion was enhanced after OVA challenge. In addition increased expression of mRNA was found for the purinergic receptors P2Y₆ and A_2B and the Cl^- channel CFTR. AMP induced Cl- secretion was not detectible in trachea of CD73 -/-, indicating that formation of extracellular adenosine in the trachea is due to degradation of AMP through ecto-5´-nucleotidase. Enhanced sensitivity to purines on Cl^- secretion was not observed in CD73 -/- mice. Application of ATP (10 mM) facilitated mucociliary clearance in BALB/c and CD73, but was strongly induced in OVA challenged mice. In conclusion, release of ATP and increased expression of purinergic receptors during airway inflammation enforce mucociliary clearance. In addition ATP and adenosine formation by ecto-5´-nucleotidase cause acute airway inflammation. This may reflect a novel target for therapeutic intervention. This study is supported by Else Kröner- Fresenius- Stiftung, SFB 699 A7 and EU-FP6-2005-CH-037365.