Human sera contain anti-IgE autoantibodies with diverse biological functions in vitro. Opposite functions can be shown for triggering of IgE-mediated histamine release from human basophils in terms of anaphylactogenic or nonanaphylactogenic autoantibodies. Furthermore, autoantibodies are either capable of removing IgE from the surface of CD23-positive cells of binding more IgE to such cells. A similar dichotomy seems also to exist for the effect of autoantibodies on human IgE mRNA synthesis as well as IL-4-induced proliferation of human mononuclear cells. Thus, anti-IgE autoantibodies may represent a key factor in the manifestation and the development of allergic disease.