Whole-body copper metabolism is difficult to study in human subjects. However, the use of isotopic tracers and kinetics modeling has added a dimension beyond what can be learned in humans by direct measurement. Mechanisms regulating total body copper seem to be strong, given the relatively small and constant body pool, but they are not yet well understood. The efficiency of copper absorption varies greatly, depending on dietary intake. Changes in efficiency of absorption help to regulate the amount of copper retained by the body. In addition, endogenous excretion of copper into the gastrointestinal tract depends heavily on the amount of copper absorbed. When dietary copper is high and more is absorbed, endogenous excretion increases, protecting against excess accumulation of copper in the body. When intake is low, little endogenous copper is excreted, protecting against copper depletion. Regulation is not sufficient with very low amounts of dietary copper (0.38 mg/d) and appears to be delayed when copper intake is high. The use of isotopic tracers and kinetic modeling should aid in elucidating the regulatory mechanisms.