T cell and natural killer (NK) cell functions are regulated by triggering of activating and inhibitory cell surface receptors. Here, we have studied the expression profile and predicted inhibitory function of mouse "killer cell lectin-like receptor G1" (KLRG1) on CD8 T cells. KLRG1 was present on 1 - 3 % of adult splenic CD8 cells that expressed CD8alpha beta heterodimers as well as a polyclonal TCR Vbeta repertoire indicative of conventional CD8 cells. The majority of KLRG1(+) CD8 cells belonged to the memory pool as determined by extensive phenotypic marker analysis. Spontaneous IFN-gamma production by approximately 20 % of KLRG1(+) CD8 cells identified them as pro-inflammatory effector cells. In contrast to NK cells, Ly49 and KLRG1 expression on CD8cells was found to be mutually exclusive. Therefore, distinct programs regulate KLRG1 expression in CD8 and NK cells. Finally, we provide evidence that KLRG1 triggering interferes with TCRalpha beta-mediated Ca(++) mobilization and cytotoxicity, raising the possibility that KLRG1 functionally participates in down-regulation of CD8 T cell responses.