Male Lewis rats were exposed from 1 to 6 weeks (3 hr/day, 5 days/week) to a Cd aerosol (1.6 mg Cd/m3). After the first week, there were significant elevations in airway amounts of lactic dehydrogenase, alkaline and acid phosphatase, protein, and polymorphonuclear leucocytes. After 2 weeks of exposures, airway cytological and biochemical alterations intensified and pulmonary histopathology was observed. The severity of pulmonary injury did not progress beyond this point, although Cd continued to accumulate in the lung in a linear fashion. During the next 3 weeks of exposures, airway alterations diminished and lung histology became normal, suggesting that pulmonary adaptation to Cd might have occurred. Cd-binding proteins, with properties similar to hepatic metallothionein (MT), were isolated from the lungs of Cd-exposed animals. Pulmonary MT quantities increased significantly with repeated exposure to Cd. Sequestration of Cd by MT may be involved in the partial resolution of the lung injury. Translocation of Cd to the liver and kidney also occurred following inhalation exposure. Prior Cd inhalation exposure increased Cd translocation to the kidney, but not to the liver. Liver and kidney Cd burdens increased during the 6 weeks of Cd exposure. MT values also rose but hepatic MT quantities increased faster and to a greater extent than renal MT quantities.