Natural killer (NK) cells and activated CD8 cells both express cytotoxic activity and produce substantial levels of IFN‐γ in response to viral and bacterial infections. In the case of NK cells, cellular activation and IFN‐γ expression are regulated by an interaction between NK receptors and MHC class Ib molecules, including HLA‐E/Qa‐1. We have used soluble tetrameric complexes of the murine class Ib molecule Qa‐1 to define the significance of this interaction for CD8 cells. We find that all CD8 cells express a receptor for Qa‐1 and that ligation of this receptor by Qa‐1 results in up‐regulation of IFN‐γ production.