Paradoxically, the thymus undergoes severe age-associated atrophy from puberty leading to increased susceptibility to disease and often fatal infections. However, despite its reduced capacity, the aged thymus retains the essential stromal elements, albeit grossly disorganised architecturally. Clinically, this loss of thymic function leads to severe morbidity and often mortality following HSC transplantation. Sex steroids have been show to be the major mediator of thymic atrophy. We have shown that of blocking sex steroids profoundly enhances thymus function and immune capacity in adult and aged mice. This involved triggering proliferation of the early thymocyte precursors, reduction of apoptotic cells and restored thymic architecture. In BMT models, sex steroids ablation caused a significant enhancement of BM function and levels of HSC. Clinical trials using an LHRH agonist to ablate sex steroids in patients receiving allogeneic or autologous peripheral blood HSC transplantation (PBST) have shown firstly improved engraftment within the first month posttransplant. In addition there was a significant increase in CD34+ stem cell numbers and NK cells. Importantly there was an increase in total and naive (CD45RA+CD62L+CD45RO-; TREC+ )T cell numbers in the blood post-transplant compared to controls. Patients receiving the LHRH-A treatment also demonstrated a significantly increased in vitro proliferative responsiveness to TCR stimulation. These studies set a fundamentally new approach for the treatment of many clinically based T-cell disorders.