We describe the development and function of the peripheral lymphoid system of mutant mice rendered deficient in either α β or γδ T cells via targeting of TCR genes In embryonic stem cells. In the spleen of α β T cell-deficient mice, γδ T cells do not compensate in numbers for the lack of α β T cells, but B cells do. α β T cell-deficient mice are unable to mount an antibody response to ovalbumln and do not reject skin allografts. Natural killer cell function is not impaired in any of the mutant mice. TCR mutant mice will prove useful in dissecting differential functions of α β and γδ T cells in vivo.