Copper is a trace element that is crucial for the function of enzymes involved in processes such as mitochondrial respiration, neurotransmitter processing and antioxidant defense. As copper can be toxic in its free form, its cellular uptake is tightly regulated. On page 1315, Michael Petris and colleagues explore how environmental stress affects copper transport into the secretory pathway in mouse macrophages. They show for the first time that hypoxia induces an increase in copper uptake, which correlates with an increase in the expression of CTR1, a copper importer, and an increase in the expression and trafficking of ATP7A, a copper transporter found in the Golgi. In addition, ATP7A-mediated copper delivery is shown to be required for the optimal activity of the copper-dependent enzyme ceruloplasmin, the expression of which is increased in response to hypoxia. Interestingly, in contrast to the increased expression of CTR1 and ATP7A, the expression of other copper-binding proteins in the mitochondria and cytoplasm decreases in response to hypoxia. This represents the first evidence that pathways of intracellular copper distribution can be differentially regulated in response to environmental stress, and suggests that copper might be selectively distributed to the secretory pathway in response to hypoxia.