Metallothionein (MT) levels were measured by radioimmunoassay in lungs of animals exposed 0, 3, and 6 days to 85% oxygen. MT levels increased with duration of exposure from 112.0 ng/lung in sham air control animals to 872.6 ng/lung in animals exposed for 6 days to oxygen. Gel chromatographic analysis of lung homogenates from oxygen-exposed animals revealed the presence of a copper- and zinc-binding component with an approximate molecular weight of 12,000 Da. It was heat stable and cross-reacted with anti-MT. The induction of pulmonary Cu/Zn-thionein was accompanied by an acute phase response, characterized by elevated serum Cu and ceruloplasmin levels and depressed serum Zn. Total lung Cu and Zn also increased, perhaps as a consequence of normal repairative processes necessitated by the oxidant injury. Increased adrenal weight and coincident thymic atrophy in oxygen-exposed animals suggested the participation of adrenocorticosteroids in the induction process.