Hephaestin (Heph) is a multicopper ferroxidase (MCF) important for the export of inorganic dietary iron from vertebrate intestinal cells to the blood. The gene is mutated in the sex‐linked anemia (sla) mouse and results in severe iron deficiency. However, sla mice still retain some hephaestin ferroxidase activity, and they survive, breed, and their anemia improves with age. In order to clarify the role of Heph in intestinal iron absorption, we have used the cre‐lox system to generate a knockout mouse model with intestinal ablation of Heph. The knockout mice are small and anemic compared to wild‐type littermates, and mice born to knockout mothers exhibit truncal hair loss that improves after weaning. The viability of these mice supports the hypothesis that other mechanisms exist, MCF‐dependent or not, for iron acquisition. These mice will serve as a valuable tool to study the role of hephaestin and other proteins involved in intestinal iron transport. Support: NIH (CDV, JLD), NSF (BKF)