Two series of experiments are presented indicating that FcγII receptors can interfere with the antigen receptor-induced signaling on T cells. It has been previously described that a 13 amino acid motif on the cytoplasmic portion of FcγII β 1 can abrogate the antigen receptor-initiated signals mediated through consensus motifs present on the cytoplasmic portion of Igα and Igβ chains. Similar activating motifs are crucial to T-cell receptor (TCR) signaling. A splenic γ δ T-cell hybridoma that expressed the FcγRII β 1 receptor helped to establish that this receptor can also interfere with TCR-induced activation. The cytoplasmic portion of human FcγRIIa has an activation motif similar to the activation motifs present on the TCR. Using a transgenic mouse in which the T cells express the human FcγRIIa transgene, we demonstrated that despite the common activation motif, the TCR and human FcγRIIa-induced signals are different. Additionally, the human FcγRIIa expressing T cells exhibit an enhanced TCR response both in vitro and in vivo.