We have characterized a prominent (15-20%) thymocyte population expressing CD4 at a high and CD8 at a low level (CD4+8lo) in mice transgenic for a T cell receptor (TCR) restricted by major histocompatibility complex (MHC) class I molecules. The results demonstrate that the CD4+8lo population is an intermediate stage between immature CD4+8+ and end-stage CD4+8- thymocytes and that the survival of these cells crucially depends on the successful interaction of the transgenic TCR with self MHC class I molecules. In addition we demonstrate that the avidity of the interaction between TCR and self MHC class I molecules determines whether CD4+8lo thymocytes are found in significant numbers in this transgenic model. Our findings support a selective and multi-step model of T cell differentiation in the thymus.