Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, and they differ functionally and phenotypically from the rest of the naïve T-cell pool. RTEs are present in the peripheral T-cell pool throughout life but are the most common subset of T cells in neonates and adults recovering from lymphoablation. Using a murine model to study the homeostasis of RTEs, we show that under lymphoreplete conditions, RTEs are at a competitive disadvantage to already established mature naïve (MN) T cells. This disadvantage may be caused by a defect in survival, because RTEs may transduce homeostatic signals inefficiently, and their ability to survive is enhanced with increased expression of IL-7 receptor or B-cell lymphoma 2 (Bcl-2). Conversely, under lymphopenic conditions, enhanced proliferation by RTEs allows them to out-compete their MN T-cell counterparts. These results suggest that in times of need, such as in neonates or lymphopenic adults, RTEs perform well to fill the gaps in the peripheral T-cell pool, but when the periphery already is full, many RTEs are not incorporated into the pool of recirculating lymphocytes. R ecent thymic emigrants (RTEs) are the youngest subset of naïve T cells, those that recently have entered the lymphoid periphery after development in the thymus. RTEs maintain T-cell diversity in the periphery (1), a particularly important contribution in the very young and in adults recovering from lymphopenia.The original paradigm held that the thymus minted fully functional T cells. However, it is becoming clear that RTEs in both humans and mice undergo postthymic maturation in the lymphoid periphery (2-6) before joining the mature naïve (MN) T-cell pool. RTEs and MN T cells differ in surface phenotype, and, as compared with MN T cells, stimulated RTEs generally proliferate less and secrete less cytokine. Studying RTEs has been facilitated by the characterization of a transgenic (Tg) model system (7) that allows unambiguous identification and live-cell purification of this subset. In mice Tg for GFP under control of the recombination activating gene 2 promoter (RAG2p-GFP Tg mice), RTEs are GFP + peripheral T cells (2). The GFP label is brightest in the youngest RTEs (8) and decays over time until it can no longer be detected on T cells that have been in the lymphoid periphery for more than 3 wk (2).Throughout life, the peripheral T-cell pool is maintained at a relatively constant size despite continuous turnover and thymic export of about 1 × 10 6 cells per day (9, 10). The T-cell pool is maintained at a size large enough to protect adequately against pathogens, with estimated 1 × 10 6 antigen specificities (11), but small enough to avoid taxing the host's resources. Homeostasis is maintained by competition for two limiting factors, IL-7 and MHC loaded with self-peptides (12, 13).Lymphopenia occurs in humans in a variety of clinical and disease settings, including after stem cell transplantation, chemotherapy, and HIV infection. Under lymphopenic conditions, the remaining peripheral ...