Drug reaction with eosinophilia and systemic symptoms is a rare and potentially serious skin adverse reaction, with fever, polymorphous skin rash, facial edema, and/or lymphadenopathy. Reactivation of human herpes virus type 6 has been associated with a more severe and/or prolonged course. A 22-month-old infant under phenobarbital treatment developed erythematous-papular lesions, fever, leukocytosis, elevated C-reactive protein, and abnormal liver tests. The skin biopsy was compatible with an adverse drug reaction. Treatment with systemic corticosteroids and intravenous immunoglobulin had no response. Polymerase chain reaction for human herpesvirus type 6 was positive, and cyclosporine plus prednisone wasstarted with a good response. There islittle evidence for the use of cyclosporine in adults when systemic corticosteroids are ineffective. This is the first report of pediatric drug reaction with eosinophilia and systemic symptoms treated with cyclosporine, which could be an effective alternative or an adjunct to systemic corticosteroid therapy unresponsive to conventional treatments.