The discovery that the high affinity IgE receptor (Fc epsilon RI) is expressed on APCs of patients with atopic diseases raised the possibility that the functional importance of Fc epsilon RI in the pathogenesis of atopy may extend beyond its role in type I allergic reactions. Here we show that, following removal of in vivo-bound IgE by lactic acid treatment, targeting of allergens to monocytes by Ag-specific IgE critically depends on Fc epsilon RI expression. Even more importantly, lactic acid-treated, monocyte-enriched PBMCs present allergen to T cells 100- to 1000-fold more effectively if the allergen has been targeted to Fc epsilon RI on these cells via allergen-specific IgE. This mechanism may critically lower the atopic individual's threshold to mount allergen-specific T cell responses capable of promoting IgE production and delayed-type hypersensitivity reactions.