We appreciate the interest that Frazer and colleagues have shown in our work. However, in contrast to their interpretation, the purpose of our initial paper1 was not to define the possible role of Cybrd1 (duodenal cytochrome b [Dcytb]) in intestinal iron absorption but rather to determine whether it is essential for the procurement of iron for utilization and storage in vivo. Our results clearly showed that it is not essential in129S6/SvEvTac mice, whether they were fed a standard lab diet or an iron-deficient diet. Frazer and his coworkers are correct that our standard chow contains ferrous iron, possibly eliminating the need for an enzymatic ferric reductase. However, as we reported, 1 animals lacking Cybrd1 maintained iron stores comparable to wild-type mice after 8 weeks on an iron-deficient diet. In unpublished studies, we continued Cybrd1/ mice on the iron-deficient diet for 6 months. Even under these conditions, their tissue iron stores and hematologic parameters were indistinguishable from wild type. Clearly, Cybrd1 is not essential for viability, for erythroid iron assimilation, or for maintenance of liver iron stores. While our data do not rule out a defect in intestinal iron absorption in Cybrd1/ mice, they argue against a major role for Cybrd1 in vivo. For comparison, mice lacking the iron transporter Slc11a2 (divalent metal transporter 1 [DMT1]) in the intestine show a very severe reduction in liver iron stores and profound anemia that is undoubtedly due to a failure of intestinal iron absorption. 2 We have not yet attempted to address whether Cybrd1 facilitates intestinal iron absorption. Other ferric reductases have been identified recently, 3 raising the possibility that there may be functional redundancy in dietary iron reduction. Future experiments should answer these questions.