Although hemolytic uremic syndrome (HUS) is usually idiopathic, it follows a number of infections. The pathogenesis of post-infectious HUS is endothelial cell damage by either circulating endotoxin or exotoxin. Diphtheria exotoxin has never been implicated in HUS. We report HUS following diphtheria infection in a 9 yr old un-immunized white female admitted with a short history of sorethroat and thrombocytopenia. There were hemorrhages in sclera, gums and left tonsillar area and a grayish exudate on right tonsil. Laboratory values revealed Hgb 14.4 g/dl, decreasing to 7.6 g/dl, WBC/26,900 mm3, platelet count 7,000/mm3. Bone marrow examination revealed normal megakaryocytes. She was oliguric with BUN 214 mg/dl, serum creatinine 12.4 mg/dl and serum uric acid 19.2 mg/dl. Despite peritoneal dialysis, red cell and platelet transfusions and exchange transfusion she expired. A postmortem examination was refused. A throat culture done on admission grew corynebacterium species which was later confirmed to be toxigenic C. diphtheriae. Diphtheria exotoxin inactivates an enzyme in cytoplasm which is necessary for peptide chain elongation. This may have interfered with prostacyclin synthesis thereby allowing the development of HUS.