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Context: Titanium dioxide (TiO2) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases. Objective: We investigated whether single or repeated exposure to TiO2 could aggravate inflammatory responses in naïve mice and mice with ovalbumin (OVA)-induced airway inflammation. Methods: Exposure to aerosolized TiO2 was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24 h after the last OVA challenge or TiO2 exposure. Results: A single exposure of TiO2 had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naïve animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO2 was given before allergen challenge. Repeated exposures to TiO2 during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO2 during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight. Conclusion: We conclude that inhalation of TiO2 may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma. [ABSTRACT FROM AUTHOR]