Scope: Factors such as food processing, the food matrix and antacid medication may affect the bioaccessibility of proteins in the gastrointestinal tract and hence their allergenic activity. However, at present they are poorly understood.Methods and results: Roasted peanut flour was incurred into either a chocolate dessert or cookie matrix and bio-accessibility assessed using an in vitro digestion system comprising a model chew and simulated gastric and duodenal digestion. Protein digestion was monitored by SDS-PAGE and immunoreactivity analysed by immunoblotting and immunoassay. IgE reactivity was assessed by immunoassay using serum panels from peanut-allergic subjects. Roasted peanut flour proteins proved highly digestible following gastro-duodenal digestion even when incurred into a food matrix, with only low molecular weight polypeptides of Mr<8 kDa remaining. When gastric digestion was performed atpH 6.5 (simulating the effect of antacid medication) peanut proteins were not digested; subsequent duodenal digestion was also limited. IgE reactivity of the major peanut allergens Ara h 1, Ara h 2 and Ara h 6, although reduced, was retained after oral-gastro-duodenal digestion irrespective of digestion conditions employed.Conclusion: Peanut allergen bio-accessibility was unaffected by the dessert or cookie matrices whilst high intra-gastric pH conditions rendered allergens more resistant to digestion.