Severe adverse cutaneous reactions were documented in two dogs with acute skin lesions and systemic signs after exposure to several oral and injectable drugs. Because of the high morbidity and mortality rates of many severe cutaneous drug reactions and a poor response to supportive care, wound management, and conventional immunosuppressive therapy, human intravenous immunoglobulin (IVIG) was infused on 2 consecutive days (1 g/kg per day) after informed consent was received. Human IVIG, with supportive care, resulted in rapid resolution of dermatological and systemic signs in both dogs; this treatment may be considered in other cases of severe cutaneous drug reactions.