We report the case of a 58-year-old man who suffered from a generalized and intolerable itching one month after starting treatment with colchicine, amiodarone, perindopril, allopurinol and spironolactone. From the start of treatment he had progressively developed erythroderma, fever, anorexia and prostration, oedema of both hands and face, hypereosinophilia (42%; 5810 eosinophils/mm3), hepatic failure (including cholestatic jaundice, cytolysis, coagulation abnormalities and hypoproteinaemia), exocrine pancreatic failure (with severe steatorrhoea), renal failure, metabolic acidosis, aggravation of pre-existing cardiac insufficiency and oedema of the lower extremities. All medications were stopped and the condition improved slowly until complete remission was reached 4 months later. Patch-testing was performed, including the various drugs. All the tests (including components of the vehicles) were negative, except for spironolactone, which gave a strong positive reaction. Ten controls in healthy volunteers were negative. The diagnosis of drug rash with eosinophilia and systemic symptoms (DRESS) induced by spironolactone was made. This is the first report of DRESS due to spironolactone