The Fc receptor with low affinity for IgG (FCGR3, or CD16) is encoded by 2 nearly identical genes, FCGR3A and FCGR3B, resulting in tissue-specific expression of alternative membrane-anchored isoforms. FCGR3A, it is also known as CD16a, encodes a transmembrane protein expressed on activated monocytes/macrophages, natural killer (NK) cells, and a subset of T cells. CD16a / FCGR3A is a receptor expressed on NK cells that facilitates antibody dependent cellular cytotoxicity (ADCC) by binding to the Fc portion of various antibodies. CD16a / FCGR3A also has a broader function. CD16a / FCGR3A is directly involved in the lysis of some virus-infected cells and tumor cells by NK cells, independent of antibody binding. Cross-linking of CD16a / FCGR3A on NK cells resulted in increased intracellular Ca2+ levels and a cascade of biochemical events similar to those activated by the T cell receptor. CD16a / FCGR3A on human NK cells is a lysis receptor that mediates the direct killing of some virus infected and tumor cells, independent of antibody ligation.