Long before the discovery of IgE it was reported that human dander extract can elicit immediate-type skin reactions in patients with severe atopy and that this skin sensitivity can be passively transferred with serum. Several recent findings have rekindled the interest in this phenomenon and led to the concept that IgE autoreactivity may play a pathogenetic role in severe and chronic forms of atopy. The elucidation of the nature of several environmental allergens has revealed striking structural and immunologic similarities with human proteins. It was also reported that patients predominantly with severe and chronic manifestations of atopy (eg, atopic dermatitis) contain IgE autoantibodies against a wide variety of proteins expressed in histogenetically unrelated human cell types and tissue specimens. Last, complementary DNAs coding for autoallergens were isolated from human expression complementary DNA libraries and recombinant autoallergens were produced. The autoallergens characterized to date represent mainly intracellular proteins, but some of them could be detected as IgE immune complexes in sera of sensitized patients. We suggest that at least two pathomechanisms could play a role in autoallergy. First, autoallergens may cross-link effector cell-bound IgE autoantibodies and, by release of inflammatory mediators, lead to immediate-type symptoms. Second, IgE-mediated presentation of autoallergens may activate autoreactive T cells to release proinflammatory cytokines, contributing to the magnitude of the allergic tissue reaction. (J Allergy Clin Immunol 2000;105:432-7.)