The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, is a type of drug hypersensitivity syndrome, is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute hepatic failure. In this article, the authors report a case of DRESS syndrome with severe exfoliative dermatitis with acute hepatitis associated with intake of leflunomide. Rapid diagnosis with withdrawal of offending agent is crucial for survival of these cases.