Hepcidin regulates iron homeostasis by inhibiting the release of iron from enterocytes and RE macrophages. To achieve this effect, it is proposed that hepcidin binds to the ferroportin transporter, triggering its internalization and degradation. In the present study, we have examined the effects of hepcidin in two human cell lines; Caco‐2 intestinal epithelial cells and THP‐1 macrophages. In THP‐1 cells there was a rapid (within 4h) decrease in ferroportin protein expression following exposure to 1μM hepcidin (control 1.1 ± 0.05 a.u.; +hepcidin 0.5 ± 0.06 a.u., P<0.001). The inhibitory effect of hepcidin on THP‐1 ferroportin levels was dose‐dependent with an IC 50 of approximately 300nM hepcidin. In contrast, there was no effect of hepcidin on ferroportin expression in Caco‐2 cells, even when the hepcidin concentration was elevated to 3μM (control 1.0 ± 0.28 a.u.; +hepcidin 1.4 ± 0.26 a.u. P>0.1). These data support the hypothesis that iron‐recycling macrophages are more sensitive than enterocytes to changes in hepcidin levels, and is fully consistent with the paramount importance of macrophages in maintaining the supply of iron for erythropoiesis. This work was funded by the Biotechnology and Biological Sciences Research Council.