Given the importance of immunoglobulin (Ig) E in mediating type I hypersensitivity, inhibiting IgE production would be a general way of controlling allergic disease. The low-affinity IgE receptor (FceRII or CD23) has long been proposed to be a natural regulator of IgE synthesis. In vivo research supporting this concept includes the observation that mice lacking CD23 have increased IgE production whereas mice overexpressing CD23 show strongly suppressed IgE responses. In addition, the finding that mice injected with monoclonal antibody directed against the coiled-coil stalk of CD23 have enhanced soluble CD23 release and increased IgE production demonstrates that full-length, trimeric CD23 is responsible for initiating an IgE inhibitory signal. The recent identification of ADAM10 (a disintegrin and metalloprotease) as the CD23 metalloprotease provides an alternative approach for designing therapies to combat allergic disease. Current data suggest that stabilizing cell-surface CD23 would be a natural means to decrease IgE synthesis and thus control type I hypersensitivity.