It is generally believed that the avidity of the T cell receptor for self antigen/MHC determines the fate of a thymocyte. However, it is not understood how the thymocyte distinguishes a survival signal (positive selection) from a death signal (negative selection). Recent studies from our laboratory have explored the role that thymus-produced glucocorticoids may play in influencing thymocyte development. It appears that glucocorticoids are important and necessary at several points during thymocyte differentiation and that they may regulate antigen-specific T cell development.