A 16-year-old male patient, with a history of essential hypertension enrolled in an experimental drug protocol using allopurinol, presented to our emergency department with a 10-day history of fever. Initial laboratory evaluation revealed leukocytosis, eosinophilia, and transaminitis. After extensive work-up and exclusion of infectious and oncologic etiologies, the diagnosis of allopurinol-induced drug reaction and eosinophilia with systemic symptoms syndrome was carried out. The patient responded to administration of IV methylprednisolone, with complete resolution of symptoms and improvement of laboratory abnormalities. This case represents the first report of allopurinol-induced drug reaction and eosinophilia with systemic symptoms syndrome in a pediatric patient.