Natural killer (NK) cells part of innate immunity. NK cells have been assigned numerous functions, including the ability to serve as a bridge between innate and adaptive immunity. In evaluating NK cell function, two pathways need to be examined: their ability to kill certain tumors spontaneously and their ability to secrete cytokines, interferon-gamma (IFN-gamma), in particular. Although NK cells are distinct from T lymphocytes, a new lymphocyte subset, termed NKT cell, has been described. NKT cells express surface markers that are unique to NK cells (e.g., NK1.1) as well as markers that are unique to T cells (e.g., CD3). Most NKT cells recognize glycolipids and are thought to play an important immunoregulatory role. This chapter will detail the methodology needed for examination of NK and NKT cells in mice.