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The role of intestinal cells in copper homeostasis and storage has not been studied. Homeostasis is regulated by absorption, excretion, and storage. Copper is excreted via the bile, and it has been assumed that the increased excretion into the gastrointestinal tract when diets are high in copper was due to biliary copper. It seemed possible that some of the absorbed copper is sequestered in the intestinal cells. To test this hypothesis we measured the copper content of mucosal epithelial cells isolated from stool samples of 8 young men when consuming their usual diets and after 129 days of supplementation with 7 mg/day copper. The mean copper content of the cells, expressed as mg copper per gram of cell protein, was 0.78 versus 1.65 mg/g (SEM 0.19) (P < 0.02) when the usual and copper-supplemented diets, respectively, were consumed. In contrast to the copper content of plasma and urine, copper in intestinal cells increased significantly when intake was high. It is likely that copper was sequestered by these cells following absorption and did not get into systemic circulation. Thus, the amount of endogenous copper in stools is probably a combination of biliary copper excretion and copper sequestered in exfoliated intestinal epithelial cells. This suggests that retention of copper by the intestinal cells increases when dietary copper is high and plays a role in copper homeostasis. J. Trace Elem. Exp. Med. 16:105–108, 2003. Published 2003 Wiley–Liss, Inc. [ABSTRACT FROM AUTHOR]