Oxidative stress may be a fundamental mode of injury associated with inspired particles. To examine this, we determined the ability of three carbon black particles (CBPs; M120, M880, and R250) and two forms of silicon dioxide, amorphous (Cabosil) and crystalline (DQ12) quartz, to deplete epithelium lining fluid antioxidant defenses. Single and composite antioxidant solutions of uric acid, ascorbic acid (AA), and reduced glutathione (GSH) were examined in the presence of particle concentrations of 150 microgram/ml. Uric acid was not depleted by any particle considered. AA was depleted in a near-linear fashion with time by the three different CBPs; however, AA depletion rates varied markedly with CBP type and decreased in the presence of metal chelators. An initially high GSH depletion rate was noted with all CBPs, and this was always accompanied by the appearance of oxidized glutathione. Exposure to Cabosil or DQ12 did not result in the loss of GSH. Together, these data demonstrate that particle type, size, and surface area are all important factors when considering particle-antioxidant interactions in the airways.