The y subunit of immunoglobulin Fc receptors is an essential component of the high-affinity receptor for IgE (FcERI) and the low-affinity receptor for IgG (FcyRIII) and is associated with the high-affinity receptor for IgG (FcyRI) and the T cell receptor-CD3 complex. It is required for both receptor assembly and signal transduction. Targeted disruption of this subunit results in immunocompromised mice. Activated macrophages from y chain-deficient mice unexpectedly lack the ability to phagocytose antibody-coated particles, despite normal binding. Defects in NK cell-mediated antibody-dependent cytotoxicity and mast cellmediated allergic responses are evident in these animals, establishing the indispensable role of FcRs in these responses. However, loss of y chain does not appear to perturb T cell development, since both thymic and peripheral T cell populations appear normal. These mice thus represent an important tool for evaluating the role of these receptors in humoral and cellular immune responses.