A subset of CD8+ T cells express the natural killer cell receptors CD94:NKG2A or CD94:NKG2C. We found that although many CD8+ T cells transcribe CD94 and NKG2C, expression of a functional CD94:NKG2C receptor is restricted to highly differentiated effector cells. CD94:NKG2A is expressed by a different subset consisting of CCR7+ memory cells and CCR7– effector cells. Since NKG2A can only be induced on naive CD8+ T cells while CD94– memory cells are refractory, it is likely that commitment to the CD94:NKG2A+ subset occurs during the first encounter with antigen. CCR7+CD94:NKG2A+ T cells recirculate through lymph nodes where upon activation, they produce large quantities of IFN-γ. These cells occur as a separate CD94:NKG2A+ T cell lineage with a distinct TCR repertoire that differs from that of the other CD8+CD94– T cells activated in situ.