The demonstration that human IgE recognizes both exogenous allergens and structurally related human proteins has led to the hypothesis that IgE autoreactivity may be a pathogenic factor in atopic diseases. To determine the frequency of occurrence as well as the disease specificity of this phenomenon, we tested sera from patients with atopic diseases and, for control purposes, from persons with immunologically mediated disorders for serum IgE reactivity with nitrocellulose-blotted human proteins. We found that 12 of 20 sera from atopic patients with pronounced skin lesions contained Western blot-detectable IgE antibodies. Patients suffering predominantly from allergic rhinoconjunctivitis as well as control individuals failed to display serum IgE autoreactivity, but occasionally exhibited elevated serum IgE levels. The molecular weights of the IgE-defined autoantigens ranged predominantly from 10 to 100 kDa. Whereas some of these were expressed in only certain cell types, others were detected in histogenetically different cells. Our results suggest that IgE autoimmunity occurs frequently in atopic dermatitis patients and may be of pathogenic relevance for the chronicity of skin manifestations typical of this disease.