The correction of anemia in dialysis patients with erythropoietin (EPO) can be frustrated by insufficient iron. To address this effect, we preloaded candidate EPO patients with intravenous iron in the early 1990s. Preloading with 900–1,525 mg of iron yielded the following results: 70% of patients had increasing hematocrits (HCTs) without EPO, and 40% of patients had HCTs greater than 30%. Apparent lack of iron led to blood loss studies. Routes evaluated were blood sampling, dialyzer clotting, blood in the dialyzer circuit and postdialysis bleeding. Projected annual losses were between 2,516 and 5,126 ml, depending on circuit and posttreatment losses. In terms of red cell loss, the results are comparable to those in the early days of dialysis before the introduction of current technology. Extension of these studies to daily dialysis predicts possible losses with this 6 times a week therapy of between 4,663 and 9,884 ml per year.