Immunoglobulin Fc receptor (FcR)γsubunit is a component of low affinity receptor for IgG, FCγRIII, as well as high affinity receptor for IgE, FcεRI. This subunit is required for efficient surface expression of these FcRs on various cells in immune system. The FcRγ-deficient mice, generated by gene targeting in embryonic stem cells, exhibit multiple defects in FcR-mediated effector cell responses, including absence of phagocytic activity against opsonized red blood cells by activated macrophages, loss of antibody-dependent cell-mediated cytotoxicity manifested by IL-2-induced splenic NK cells, and unresponsiveness of mast cells to crosslinking of IgE on these cells. These results demonstrate an indispensable role of FcRγfor functional expression of FcRs, and clearly indicate the importance of FCγRIII as well as FcεRI for these effector functions. Since FcRγ-deficient mice is unable to mount the type II and type III hypersensitivity reactions, it is suggested that FcRs play pivotal roles in initiating these reaction cascades. The mutant mice should prove to be useful in evaluating FcRs in various humoral and cellular immune responses, and in developing new strategies for treatment of immunodeficiency as well as autoimmune disorders.