The effects of feeding rats high levels of dietary zinc (240 mg Zn/kg diet) on the activities of the copper-requiring metalloenzymes: ceruloplasmin (Cp), cupro-zinc superoxide dismutase (SOD) and cytochrome c oxidase (CCO) were determined. These were compared with those seen during copper deficiency (induced by feeding 0.6 mg Cu/kg diet). The activities of Cp in serum, Cu-Zn SOD in liver and heart, and CCO in heart were significantly reduced in both the high zinc and copper-deficient groups by 2 weeks, when compared to the activities seen in rats fed the control diet (6 mg Cu, 30 mg Zn/kg diet). In animals fed the high zinc diet, the reduction in heart CCO activity followed the decrease seen in heart copper concentration, whereas in blood and liver, the reductions in Cp and SOD activities, respectively, were greater than the reductions seen in copper concentration. Thus, the results of this experiment demonstrate that with high dietary zinc, the reductions seen in the activity of copper-requiring metalloenzymes were similar to those seen during copper deficiency.