THE Ets-1 proto-oncogene¹ is a member of the Ets family of eukaryotic transcription factors^2á¤-7. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals^4,5,8,9. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice^10,11 and is regulated during both thymocyte development¹¹ and T-cell activation^{*12, 13}. To study the role of Ets-1 in T-cell development and function we have used theRAG-2^-/- complementation system¹⁴ and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1^-/- ).Ets-1^-/- -RAG-2^-/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells.Ets-1^-/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-α/β. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro. These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.