Background Asthma is characterized pathologically by structural airway changes termed airway remodelling. These are associated with worse long term clinical outcomes. As inhalation allergen challenge in atopic asthma induces eosinophilic airway inflammation and extracellular matrix changes, and a reduction in airway eosinophils has been reported to reduce certain markers of airway remodelling, these tissue structural changes have been considered a consequence of eosinophilic airway inflammation. However, bronchoconstriction generates excessive mechanical forces within the airways that distort tissue cells and within other organs mechanical forces induce tissue remodelling. In vitro studies of airway epithelial cells, in a variety of models, have shown that ex vivo compression of the airway epithelium results in changes which mimic those identified and associated with remodelling in vivo. We therefore hypothesized that following allergen exposure in vivo in asthma that the induced airway narrowing may in itself be a sufficient stimulus for the development of airway remodelling and that this response is not solely dependent upon induced airway eosinophil recruitment. As asthma is a disease of repeated bronchoconstriction the relevance of these in vitro findings has been evaluated in asthma. Methods 48 asthmatics were randomly assigned to one of 4 challenge protocols involving 3 challenges at 48 hr intervals: allergen challenge (bronchoconstriction and eosinophilic airway recruitment), methacholine (bronchoconstriction without eosinophilic inflammation), saline (no bronchoconstriction) and salbutamol followed by methacholine (no bronchoconstriction), to control for any non-bronchoconstrictor effects of methacholine. Bronchial biopsies for histochemical evaluation of airway remodelling were obtained at bronchoscopy before and 4 days after completion of the challenges. Results Allergen and methacholine induced similar immediate bronchoconstriction. Inflammation increased only in the allergen group, with increases in bronchoalveolar lavage eosinophils (p=0.01), eosinophil cationic protein (p=0.002) and tissue eosinophils (p=0.05), whilst both allergen and methacholine groups showed significant induction of airway remodelling not seen in the 2 control groups. Sub-basement membrane collagen thickness (p<0.001), epithelial mucus staining (p=0.003) and cell division in the epithelium (p=0.001) and the submucosa (p<0.001) all increased as did epithelial TGF-β immunoreactivity (p<0.01). There were no differences between the allergen and methacholine groups. Conclusions Bronchoconstriction in the absence of induced airway inflammation is sufficient to induce airway remodelling in asthma. These findings have important implications for the management of asthma.