The receptor with high affinity for immunoglobulin E (IgE) on mast cells and basophils is critical in initiating allergic reactions. It is composed of an IgE-binding α subunit, a β subunit, and two γ subunits. The human α subunit was expressed on transfected cells in the presence of rat β and γ subunits or in the presence of the γ subunit alone. The IgE binding properties of the expressed human α were characteristic of receptors on normal human cells. These results now permit a systematic analysis of human IgE binding and a search for therapeutically useful inhibitors of that binding.