Diphenylhydantoine is a drug frequently used in the treatment of epilepsia. In rare occasions, it produces a mulsisystemic manifestation characterized by fever, lymphadenopathy, hepatitis, eosinophilia and desquamative cutaneous eruption, which typically develops within 4-8 weeks after the beginning of the treatment. Mortality rates may reach up to 40% in patients with severe hepatic affection, although the response to steroid therapy is usually frequent. We present the case of a patient which developed a syndrome of hypersensibility to diphenylhydantoine with mononucleosic manifestations, icteric hepatitis and exfoliative dermatitis, who completely recovered a few days after his hospitalization.