A study has been made of the distribution of copper in the kidneys of copper-poisoned sheep, containing up to 240 microgram copper/g fresh cortex. About 64% of the copper in the cortex was present in the cytosol and 75% of this occurred in a form with molecular weight of approx. 12 000. This was partially purified by gel filtration on Sephadex G-75 and Bio-Gel P.10 and ion exchange chromatography on DEAE Sephadex A-25 to give three sub-fractions, which also contained zinc. The amino acid composition, copper content and chromatographic behaviour of these proteins indicated that they were copper-thioneins. No significant amounts of the proteins were detected in the plasma or erythrocytes of the copper-poisoned sheep when they were undergoing the haemolytic crisis typical of this syndrome. It is concluded that metallothionein constitutes the major copper-binding protein in the kidneys of copper-poisoned sheep. However the rapid accumulation of the protein in the kidney, and the development of kidney damage, are unlikely to have arisen from the release of the intact copper-protein from the liver and its transport via the blood to the kidneys.