This research is designed to explore the role of IgE-mediated reactions to foods in the pathogenesis of atopic dermatitis (AD) and potential mechanisms involved. Despite considerable lay and medical interest, there is little agreement as to the prevalence, significance, or appropriate means of diagnosing food allergy. Many standard medical texts have largely dismissed food allergy as a factor in AD. However, in preliminary studies over the past 1 1/2 years, we have identified 10/22 children with severe AD and elevated serum IgE concentrations who developed distinct episodes of cutaneous pruritis and generalized macular erythema following double blind placebo-controlled oral food challenges (DBPCFC). Furthermore, we have noted that restriction of the offending food has lead to significant clinical improvement which has been accompanied by declines in serum and in vitro blood lymphocyte culture supernatant IgE concentrations. Proposed studies will evaluate the prevalence of clinically significant food allergy in children with AD. Using AD patients with food hypersensitivity diagnosed by DBPCFC, potential pathogenic mechanisms will be sought: 1) abnormal gut permeability as defined by increased antigenemia, 2) increases in circulating histamine levels, following exposure to food allergens and their association with skin symptomatology, and 3) possible aberrant gut-associated and systemic resolution of food hypersensitivity, eczematoid rash, and concomitant changes in diagnostic procedures (skin testing, RAST, antigen specific IgG) and others (presence of circulating food antigens, serum antigen specific IgA, cultured lymphocyte supernatant total and specific IgE) will be examined for their value in detecting clinically significant food allergy as defined by DBPCFC. This information should provide insight into pathogenic mechanisms involved in food allergy and guidance for appropriate therapeutic measures.