CD4+ CD8+ double-positive (DP) thymocytes, which are extremely sensitive to apoptosis, specifically up-regulate Bcl-x L to extend their lifespan. Deletion of the Bcl-x L gene leads to premature apoptosis of the thymocytes. In this study, we show that stabilization of β-catenin, a critical coactivator for T cell factor (TCF), enhances DP thymocyte survival via up-regulating Bcl-x L. Spontaneous or glucocorticoid-induced thymocyte apoptosis was associated with reduced levels of β-catenin and Bcl-x L. Transgenic expression of a stabilized β-catenin protected DP thymocytes from both spontaneous and glucocorticoid-induced apoptosis, resulting in significantly increased thymic cellularity. Compared with the wild-type mice, both protein and transcript levels of Bcl-x L were significantly increased in thymocytes of β-catenin transgenic mice. In addition, TCF-1 as well as β-catenin were able to stimulate transcriptional activity of the reporter driven by a Bcl-x L promoter. β-Catenin/TCF is thus able to act as a signal to up-regulate Bcl-x L levels in DP thymocytes, resulting in their enhanced survival.