Rationale: It is now thought that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth-factor- (TGF-) is a powerful regulator of both the tissue repair and inflammatory responses and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma. Objectives: We investigated the role of TGF- in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease. Methods: We have previously shown that intranasal administration of an HDM extract (5 days/week for 5 weeks) elicits robust Th2-polarized airway inflammation and remodeling that is associated with increased airway hyperreactivity. Here, Balb/c mice were similarly exposed to HDM and concurrently treated with a pan-specific TGF- neutralizing antibody. Measurements and Main Results: We observed that anti-TGF- treatment in the context of either continuous or intermittent HDM exposure had no effect on the development of HDM-induced airway remodeling. To further confirm these findings we also subjected SMAD3 KO mice to 5 weeks of HDM and observed that KO mice developed airway remodeling to the same extent as HDM-exposed littermate controls. Notably, TGF- neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity. Conclusions: Collectively, these data suggest that TGF- regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF- activity in the treatment of this disease.