Particle-mediated epidermal delivery (PMED) of allergen genes efficiently prevents systemic sensitization and suppresses specific IgE synthesis. We investigated in a mouse model of allergic airway disease the effect of PMED on the elicitation of local inflammatory reactions in the lung. BALB/c mice were biolistically transfected with plasmids encoding -galactosidase (Gal) as model allergen under control of the DC-targeting fascin promoter and the ubiquitously active CMV promoter, respectively. Mice were challenged intranasally with Gal-protein with or without intermediate sensitization with Gal adsorbed to aluminiumhydroxide. Subsequently local cytokine production and recruitment of IFN- producing CD8⁺ effector T cells into the airways were determined, and inflammatory parameters such as cellular infiltration in the bronchoalveolar lavage and airway hyperresponsiveness (AHR) were measured. PMED of Gal-encoding plasmids prior to sensitization significantly reduced frequencies of eosinophils in the bronchoalveolar lavage and shifted the local Th cell response from a distinct Th2 response towards a Th1-biased response. However, AHR triggered by allergen challenge via the airways was not alleviated in vaccinated mice. Most important, we show that PMED using Gal-encoding DNA without subsequent sensitization recruited Tc1 cells into the lung and caused a Th1-prone local immune response following subsequent intranasal provocation, accompanied by neutrophilic infiltration into the airways and elicitation of AHR. We conclude that robust Th1/Tc1 immune responses, although highly effective in the counter-regulation of local Th2-mediated pathology, might as well trigger local inflammatory reactions in the lung and provoke the induction of AHR in the mouse model of allergic airway disease.