The earliest thymic progenitors (ETPs) were recently shown to give rise to both lymphoid and myeloid cells. Whereas the majority of ETPs are derived from IL-7Rα-positive cells and give rise exclusively to T cells, the origin of the myeloid cells remains undefined. In this study, we show both in vitro and in vivo that IL-13Rα1 + ETPs yield myeloid cells with no potential for maturation into T cells, whereas IL-13Rα1 - ETPs lack myeloid potential. Moreover, transfer of lineage-negative IL-13Rα1 + bone marrow stem cells into IL-13Rα1-deficient mice reconstituted thymic IL-13Rα1 + myeloid ETPs. Myeloid cells or macrophages in the thymus are regarded as phagocytic cells whose function is to clear apoptotic debris generated during T cell development. However, the myeloid cells derived from IL-13Rα1 + ETPs were found to perform Ag-presenting functions. Thus, IL-13Rα1 defines a new class of myeloid restricted ETPs yielding APCs that could contribute to development of T cells and the control of immunity and autoimmunity.