specific oral tolerance induction (SOTI) is a promising approach in the treatment of severe food allergies. Different protocols have demonstrated its efficacy. Nevertheless, SOTI is still considered an experimental method and should be limited to highly controlled settings. to define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of nebulized epinephrine as a first-line treatment of respiratory reactions during in-hospital SOTI for cow's milk allergy. a retrospective study was conducted by reviewing the medical records of patients admitted for SOTI beginning in 2001. Reactions were classified as mild, moderate and severe on a partially modified Clark scale. Adverse reactions were treated following the International Guidelines with the introduction of nebulized epinephrine for level four reactions. of 209 patients, 17 were excluded due to the absence of objective reactions. The remaining 192 were classified as follows: Mild Reactions (Clark Scale 1 to 3): 100 patients received either no treatment, oral antihistamines or nebulized steroids; Moderate Reactions (Clark Scale 4): 87 patients treated with nebulized epinephrine and, depending on their symptoms, oral antihistamines, corticosteroids (nebulized, oral or IV) or nebulized beta 2 agonists; Severe Reactions (Clark Scale 5): 5 children, 4 of whom initially underwent one nebulization of epinephrine and eventually required an IM dose. The fifth patient was immediately treated with IM epinephrine due to hypotension. adverse reactions during this in-hospital SOTI protocol were frequent but easily manageable. Nebulized epinephrine can play a relevant role in the treatment of respiratory reactions.