Food-induced anaphylaxis is a life-threatening, IgE-mediated disease. No specific therapeutic recommendations, aside from the avoidance of offending foods, exist at this time. However, specific oral tolerance induction for food allergy has been investigated by several groups. In this study, specific oral tolerance induction was attempted using interferon-gamma (IFN-gamma) as an adjuvant for IgE-mediated anaphylactic food allergies. A total of 25 patients with IgE-mediated anaphylactic food allergy to milk, eggs, or wheat were selected. IFN-gamma-induced specific oral tolerance induction (ISOTI) was conducted on 10 patients, while five patients were only treated with food, five patients received only IFN-gamma therapy, and five patients did not receive any treatment. Tolerance for IgE-mediated anaphylactic food allergy was successfully induced in all patients (10/10) with ISOTI, while no patients acquired tolerance for allergenic foods in the control groups. Food-specific IgE levels were increased, and skin prick test reactions significantly decreased after the completion of ISOTI. IFN-gamma-induced specific oral tolerance induction (ISOTI) is a promisingly effective treatment for IgE-mediated anaphylactic food allergy. IFN-gamma may be an important cytokine in tolerance induction. Simultaneous allergen stimulation with nonspecific immunomodulation of IFN-gamma was essential for specific tolerance induction in IgE-mediated anaphylactic food allergy.