Signals derived from nonhematopoietic tissues are essential for normal primitive erythropoiesis in vertebrates, but little is known about the nature of these signals. In Xenopus, unidentified factors secreted by ectodermal cells during gastrulation are required to enable the underlying ventral mesoderm to form blood. Steel is expressed in the ectoderm of early Xenopus embryos and is known to regulate definitive erythroid progenitor survival and differentiation in other organisms, making it an excellent candidate regulator of primitive erythropoiesis. In this study, we tested whether steel signaling is required for primitive red blood cell differentiation in mice and frogs. We show that Xsl is expressed in the ectoderm in Xenopus gastrulae and that c-kit homologs are expressed in the underlying mesoderm at the same stages of development. We present loss of function data in whole Xenopus embryos and explants that demonstrate a requirement for ectodermally derived steel to signal through c-kit in the mesoderm to support early steps in the differentiation of primitive erythroid but not myeloid cells. Finally, we show that primitive erythropoiesis is not disrupted in mouse embryos that lack c-kit function. Our data suggest a previously unrecognized and unique function of steel/c-kit during primitive erythropoiesis in Xenopus.