Dietary copper-deficiency in rats produced a organ-specific decrease of copper content. This was paralleled by a decrease of the activity of the copper-enzyme superoxide dismutase. In liver such a decrease is partially due to the existence of an apo-form of superoxide dismutase, which can be reactivated by addition of exogenous copper to tissue extracts. These results demonstrate in vivo that superoxide dismutase is post-translationally modulated by copper in higher vertebrates as previously found for yeast and mammalian cells in culture.