There are two primary concerns in the management of patients with chronic renal failure (CRF) under hemodialysis who are receiving rHEpo for anemia - determine the ideal dose of iron and predict the response to the rHEpo therapy used to treat their anemia. The classic parameters used for monitoring iron therapy in these patients are Transferrin Saturation (TSAT %) and Ferritin (Ferr) concentration. Recently some new red cell parameters have been proposed to support these existing markers as the new research use only (RUO) tests, called Low Hemoglobin Density % (@LHD%®) and Microcytic Anemia Factor (@Maf®), produced by the LH 700 Series hematology analyzers We also have analysed the best hematological parameters to support TSAT % and Ferritin and the best predictors to predict the response to therapy. A total of 30 adult renal dialysis patients receiving EPO for treatment of anemia secondary to end-stage renal disease were enrolled over a six month period from March to August, 2006. The patients were stable with regard to dialysis treatment for at least 3 months prior to entry into the study. Patients had frequent follow up during therapy, consisting of CBC, auto-differential, automated retic %, absolute #, IRF, MRV and RUO parameters. The testing schedule followed the hospital's existing standard of care with CBC, WBC Differential and Reticulocyte measurements being performed monthly. Iron levels and iron binding capacity were measured before the beginning the study, and then monthly for the duration of the study. These and other chemistry tests were performed on the Beckman Coulter DxC and DxI chemistry and immunoassay instruments and included serum Ferritin, serum iron, TIBC, Transferrin, transferrin saturation, and CRP. A 1 ml aliquot of serum from each sample was frozen for possible additional testing later (soluble transferring receptor (sTfR), etc.). The patients' anemias were classified using their ferritin and transferrin saturation according to the KDOQI guidelines as Absolute Iron Deficiency (AID), Functional Iron Deficiency (FID) and any iron deficiency: AID or FID (any ID). CRP results were considered in the diagnosis. A response to the rHEpo therapy was defined as an increase in Hemoglobin concentration of 1 g/dL in 2 months, with a minimum increase of 0.3 g/dL per month. The patients' results were classified as responder or non-responder based on the delta Hgb and delta reticulocyte results from month to month There were 29.3% (41/140) classified as responders. Using a Mann-Whitney test, significant differences (p<0.05) were found for @LHD%, @MAF, MCH comparing patients with TSAT% <20% vs TSAT%>20% and @LHD% for patients with Ferritin <100 ng/mL vs Ferritin> 100 ng/mL) The best RBC parameters for detecting the types of anemias found in these patients were: Detection of IDA was @LHD%® (>4.7%) Detection of FID: MCH (<29.1 g/dL) and @LHD%® (>6.1%) Detection of any ID (AID or FID): @LHD%® (>4.7%) and MCH (<30 g/dL) The best parameter for the prediction of the response to therapy as indicated by an increase in Hgb is @Maf® (<9.2) with a ROC Area under the curve of 0.714. Red Cell parameters can complement the classic parameters used to detect Iron deficiency and predict the response to therapy. The value of these findings to the clinician is that when the classic chemistry parameters are borderline or indeterminate, these new red cell parameters can be use to arrive at a definitive diagnosis and ensure the correct treatment option. @ Research use only parameters