The fate of nano-TiO(2) particles in the body was investigated after inhalation exposure or intravenous (i.v.) injection, and compared with pigmentary TiO(2) and quartz. For this purpose, a 5-day inhalation study (6h/day, head/nose exposure) was carried out in male Wistar rats using nano-TiO(2) (100mg/m(3)), pigmentary TiO(2) (250mg/m(3)) and quartz dust DQ 12 (100mg/m(3)). Deposition in the lung and tissue distribution was evaluated, and histological examination of the respiratory tract was performed upon termination of exposure, and 2 weeks after the last exposure. Broncho-alveolar lavage (BAL) was carried out 3 and 14 days after the last exposure. Rats were also injected with a single intravenous dose of a suspension of TiO(2) in serum (5mg/kg body weight), and tissue content of TiO(2) was determined 1, 14 and 28 days later. The majority of the inhaled nano-TiO(2) was deposited in the lung. Translocation to the mediastinal lymph nodes was also noted, although to smaller amounts than following inhalation of pigmentary TiO(2), but much higher amounts than after exposure to quartz. Systemically available nano-TiO(2), as simulated by the i.v. injection, was trapped mainly in the liver and spleen. The (agglomerate) particle size of lung deposited nano-TiO(2) was virtually the same as in the test atmosphere. Changes in BAL fluid composition and histological examination indicated mild neutrophilic inflammation and activation of macrophages in the lung. The effects were reversible for nano- and pigmentary TiO(2), but progressive for quartz. The effects observed after 5-day inhalation exposure to nano-TiO(2) were qualitatively similar to those reported in sub-chronic studies.