To study the effects of low copper intake in older individuals, 12 postmenopausal women, aged 63.1 +/- 8.8 y, were fed a diet containing 9 micromol (0.57 mg) Cu/d for 105 d, followed by a copper-repletion period of 35 d during which the diet was supplemented with 31.5 micromol (2.0 mg) Cu/d. Plasma copper and ceruloplasmin did not change significantly during copper depletion but ceruloplasmin decreased during copper repletion. Erythrocyte superoxide dismutase activity dropped significantly during low copper intake from 3450 to 2600 U/g hemoglobin, but did not increase during copper repletion. Platelet cytochrome c oxidase activity changed significantly (P<0.0001) from 1740 to 810 U/g protein during copper depletion, then increased to 1000 U/g protein during copper repletion. Erythrocyte glutathione peroxidase activity responded similarly. Clotting factor VIII activity increased significantly during copper depletion, then dropped during copper repletion. Low copper intakes did not induce the changes in serum cholesterol and hematology generally found in copper-deficient animal models. These results indicate that a paradigm shift may be needed in evaluating copper status in adult humans. Sensitive indicators of copper include functional activities of platelet cytochrome c oxidase, platelet copper, glutathione peroxidase, and clotting factor VIII. Plasma copper, ceruloplasmin, and cholesterol are relatively insensitive indicators. Also, the recovery from mild copper depletion may require more aggressive intervention tha 2 mg Cu/d for 35 d.