The killer cell lectin-like receptor G1 (KLRG1) belongs to the family of inhibitory C-type lectins that are encoded in the NK gene complex. Similar to other inhibitory NK cell receptors, KLRG1 expression in adult peripheral blood lymphocytes is restricted to NK cells and to antigen-experienced T cells. Umbilical cord blood T cells are thought to represent an homogenous pool of naive T cells. Surprisingly, we identified substantial subsets of CD4 ( approximately 30%) and CD8 ( approximately 20%) alphabeta T cells in cord blood that expressed KLRG1. In contrast to T cells in adult, KLRG1(+) T cells in cord blood exhibited predominantly a naive CCR7(+)CD45RA(+) and CD11a(low) phenotype. After birth, KLRG1 expression in T cells from peripheral blood decreased rapidly to reappear in effector/memory T cells in adults. KLRG1(+) T cells in cord blood expressed a diverse T cell receptor beta (TCRbeta) repertoire and the cells proliferated normally, in contrast to KLRG1(+) T cells from adults. Finally, examination of T cell receptor excision circles (TREC) indicated that KLRG1 expression discriminated between cord blood T cells that differed in their post-thymic expansion rate. Thus, analysis of KLRG1 expression in cord blood revealed an unexpected heterogeneity of human T cells in newborns.