Hydrolyzed wheat proteins (HWP) can induce immediate hypersensitivity through skin contact and/or food ingestion. Such patients develop IgE against unmodified wheat proteins without allergy to wheat. Our objective was to study the IgE-reacting content of HWP. We compared the reactivity of HWP and unmodified wheat proteins with IgE from patients suffering from immediate hypersensitivity to HWP. We studied the cross-reactivity between one HWP preparation and wheat proteins using immunoblot inhibition experiments. This showed that the tested HWP carried mainly unmodified epitopes originating from wheat proteins. The size distribution of polypeptides from two HWP preparations was analyzed by size-exclusion-high performance liquid chromatography (SE-HPLC), and their reactivity with IgE was studied. This showed that they contained highly IgE-reacting high molecular weight entities, likely resulting in a rearrangement of peptides issued from gluten processes. These multiepitopic entities could explain the high immunogenicity of HWP for sensitized people.