We have used gene targeting in embryonic stem cells to generate mice with mutations in T-cell receptor (TCR) gene-alpha, TCR-beta, TCR-delta or the Recombination Activating Gene-1 (RAG-1). TCR-alpha or TCR-beta mutant mice are deficient in alpha beta T cells, but still contain gamma delta T cells and B cells. TCR-delta mutant mice are deficient in gamma delta T cells, but still contain alpha beta T cells and B cells. Mice doubly mutant for TCR-beta and TCR-delta do not have any mature T cells, but still have B cells. RAG-1 mutant mice are totally deficient in both mature T cells and B cells. Here, I describe recent studies of thymocyte development in the mutant mice, and I review experiments addressing the function of the immune system of the mutant mice.