Body iron stores should be assessed regularly and accurately during erythropoietin (r-HuEPO) replacement therapy. To evaluate the accuracy of the current tests, transferrin saturation (TSAT) and serum ferritin levels, in assessing and monitoring body iron stores, we studied 24 regular hemodialysis patients (19 males, mean age 47+/-18 years, and mean duration on hemodialysis 15+/-13 months) on regular erythropoietin therapy over a 12 month period. Patients were classified as having normal, deficient, indeterminate, or overload status depending on the values of TSAT and serum ferritin. Using TSAT and serum ferritin, iron status could be determined in 16 (67%) patients only; 12 (50%) had adequate (or normal) iron status, 3 (12.5%) had iron deficiency, and one (4.2%) had iron overload. In the remaining 8 patients, iron status was indeterminate; six patients had high serum ferritin with low TSAT (functional iron deficiency), and two patients had high TSAT values and low serum ferritin. Serum ferritin alone had very low specificity in diagnosing iron overload. In conclusion, when used together, TSAT and serum ferritin have a low sensitivity for diagnosing the iron status of CKD patients on HD. When TSAT and serum ferritin values diverge, they become unreliable in guiding iron therapy, and this set of findings generally indicates functional iron deficiency. There is a clear need to use the newer indices, like reticulocyte hemoglobin concentration and percentage of hypochromic red cells, which are more sensitive. This is likely to make the diagnosis of iron status more accurate and may reduce the requirements and frequency of iron and r-HuEPO administration.