T-cell development in the fetus and the neonate begins with immigration of fetal liver–derived stem cells into the thymus. After intrathymic T-cell maturation is complete, RTEs exit the thymus and enter the lymphoid periphery. RTEs are marked by green fluorescence in mice carrying a transgene-encoding green fluorescent protein driven by the RAG2 promoter. RTEs in the neonate enter a lymphopenic periphery and constitute the majority of peripheral T cells. In the adult, stem cells arise from the bone marrow, and after completing intrathymic maturation, the resulting RTEs exit the thymus and enter a lymphoreplete periphery, where they are surrounded by a majority of mature T cells.