The subcellular distribution of copper has been compared in the liver of normal rats and of rats subjected to bile duct ligation and daily injection of copper solutions. Using 64Cu as a tracer for copper, it was found that bile duct ligation followed by daily intraperitoneal injections of copper solutions produced a large increase in the hepatic copper content accompanied by changes in the subcellular distribution of 64Cu. In normal rats, the major portion of the hepatic 64Cu was found in the soluble fraction, but following bile duct ligation and copper injection, most of the hepatic 64Cu was associated with the formed elements of the cells, especially the lysosomes. Further fractionation of the soluble fraction on Sephadex G-200 showed that bile duct ligation and copper injection caused a change in the normal distribution of 64Cu among the proteins of this fraction. © 1969.