The inhibitory myeloid immunoglobulin receptor CD300a (IRp60) has been shown to downregulate mast cell and eosinophil activities, thereby serving as a potential target for inhibiting allergic effector cell input in allergy. Our aims were to study the expression and functional properties of this receptor in purified human basophils, cells that crucially contribute to Th2-type immunity and allergy. Basophils homogeneously expressed CD300aas well as the inhibitory receptor CD200R on their cell surface, and these expressions increased after anti-IgE stimulation. IgE-mediated basophil degranulation was also significantly inhibited by crosslinking of either CD200R or CD300a (by 90% and 50%, respectively). Inhibitory SHIP-1 phosphorylations were also induced by CD200R and CD300a, although they were not noticeably increased by IgE-dependent activation. We conclude that both CD200R and CD300a play a role in reducing IgE-mediated basophil function and may crucially govern the known differential activities of these cells in vivo.