Using an experimental model in COS-1 cells, we have examined the structural requirements for phagocytosis of IgG-sensitized cells by Fc gamma receptors. We have established that isoforms of each of the 3 classes of the Fc gamma receptors, Fc gamma RI, Fc gamma RII and Fc gamma RIII, are able to transmit a phagocytic signal in the absence of the other receptor class. Fc gamma I and Rc gamma RIIIA require a gamma-subunit for this signaling event, but Fc gamma RIIA does not. Fc gamma RIIA and the gamma-subunit associated with Fc gamma RI and Fc gamma RIIIA contain 2 copies of a conserved tyrosine-containing cytoplasmic sequence, YXXL. This sequence is important for phagocytosis and is phosphorylated on tyrosine after receptor ligation. The Fc gamma receptors Fc gamma RIIB1 and Fc gamma RIIB2 which contain only 1 copy of the YXXL cytoplasmic sequence do not include the phagocytosis of IgG-coated cells. Thus, the Fc gamma receptor isoforms differ in their ability to transmit a phagocytic signal. Structure/function studies also indicate that the Fc gamma receptors which induce phagocytosis differ in their requirements for phagocytic signaling.