DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is a drug-induced hypersensitivity syndrome that can mimic malignant lymphoma. We report a case in a 63-year-old woman who had been on sulfasalazine for 2 months to treat rheumatoid arthritis. She was admitted a few days after onset of a flu-like syndrome with a pruriginous maculopapular erythema initially involving the face, trunk, and proximal limbs; a fever of 41 degrees C; and enlargement of the liver, spleen, and several peripheral lymph nodes. Blood tests showed marked eosinophilia (9300/mm3), lymphocytosis, hyperbasophilic cells, and severe inflammation. DRESS syndrome was diagnosed. An indirect immunofluorescence assay for human herpesvirus 6 (HHV6) was positive, supporting recent HHV6 infection. Primary HHV6 infection and HHV6 reactivation have been incriminated in the genesis of DRESS syndrome. DRESS syndrome continues to carry a high mortality rate of about 10%. Drugs previously reported to cause DRESS syndrome include sulfasalazine, hydantoin, d-penicillamine, allopurinol, hydrochlorothiazide, and cyclosporine. A high index of suspicion for DRESS syndrome should be maintained in patients receiving these drugs. Serological tests for HHV6 should be performed routinely in patients with suspected DRESS syndrome, although uncertainty persists about the link between HHV6 infection and DRESS syndrome.