Background:DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a rare but severe drug reaction.Observations:A 27-year-old male with paranoid schizophrenia was hospitalized with all three diagnostic criteria of DRESS syndrome: cutaneous drug eruption, hematological abnormalities (presence of atypical lymphocytes on blood smear) and systemic involvement (generalized lymphadenopathy and hepatitis). On hospitalization the patient exhibited an unusual fever pattern of high temperatures in the morning hours and lower temperatures towards evening. In this case of a patient who needs life-long therapy, we demonstrated the value of the IFN-gamma release test, which showed positive reactivity to 3 out of 9 suspicious drugs: paracetamol, phenytoin and dypirone, allowing for more therapeutic options. After therapy, at 6-month follow-up the patient is doing well under haloperidol treatment, laboratory values including liver function tests are normal and his skin condition is good.Conclusion:We suggest that clinicians take the fever pattern of high temperatures in the morning hours and lower temperatures towards evening into account in a patient presenting with a severe cutaneous drug eruption. An interferone-gamma release test may facilitate identification of drugs responsible for the drug reaction.