Age-related thymic involution in mammals is accompanied by decreased generation of naïve T cells without significant reduction in the number of peripheral T cells. This leads to inefficient immune responses and inadequate combating of infections and other challenges to the immune system in older mammals. The molecular mechanisms that underlie this phenomenon are not known. In this report we show that expression of beta-catenin in thymocytes enhances thymic involution. The effect of beta-catenin expression is seen in all the thymic sub-populations, suggesting that an age-related developmental process is accelerated. We also show that, as in normal mice, thymic involution does not lead to a drastic reduction in splenic T cells in beta-catenin-transgenic mice. This study identifies beta-catenin expression in thymocytes as a molecular target of age-related thymic involution.