Immune hemolytic anemia (IHA) in children is commonly a self-limited disorder that can usually be managed with a combination of corticosteroid therapy and transfusions. We describe a 210/12-year-old child with severe IHA that rapidly progressed during the first 24 h of conventional treatment but that responded dramatically to plasma exchange (PE). Unique features of this case include the use of PE to avoid splenectomy, the complete and permanent clearance of detectable antibody following PE, and the rapid correction of anemia by infusing packed erythrocytes during the procedure. The role of PE in the treatment of childhood IHA is discussed. © Lippincott-Raven Publishers.