Anemia is an almost invariable part of the uremic syndrome. The majority of patients have a hemolytic component which is extracorpuscular and unrelated to immune mechanisms or splenic sequestration. In some cases mechanical injury due to abnormalities of vasculature may play a role. Metabolic and mechanical abnormalities have been described in vitro, but the relation of these to hemolysis in vitro is not clear. The rate of hemolysis seldom exceeds two or three times normal. The determining factor in the anemia is relative marrow failure such that erythropoietic response to anemic anoxia is inadequate. The defect appears to reside in the failure of the diseased kidney to produce renal erythropoietic factor (REF) to activate erythropoietin.