The IgE antibody system is among the most sophisticated of immune defense mechanisms. IgE molecules bind specifically and avidly to receptors localized on the surface of tissue mast cells and circulating basophils. These cells can produce and release several potent mediators after antigen interaction with a small number of surface-bound IgE molecules. The enormous amplification power of the IgE antibody system not only provides an important defense mechanism against parasites, but is also responsible for a number of clinical disorders. The human pathological condition most commonly associated with hyperproduction of IgE is atopy, the familial allergic disorder of immediate-type hypersensitivity to environmental allergens. In this paper Sergio Romagnani summarizes current understanding of the mechanisms involved in IgE regulation. Such studies are of primary importance in defining alterations responsible for the pathological conditions characterized by hyperproduction of IgE.