Methods for determining the responsiveness of a patient to recombinant human erythropoietin therapy are disclosed. In one approach, the method includes obtaining a volume-Hgb factor (VHf) defined as a product function of MCV and Hgb from a patient's blood sample; comparing VHf to a predetermined criterion; and reporting indication of responder if VHf meets the predetermined criterion. The method further includes using a RBC size-hemoglobin factor (RSHf) defined as a product function of MCV, MRV and Hgb, or using a function of VHf and RDW for determining the responsiveness. In another approach, the method includes using a RBC size factor (RSf) defined as a product function of MCV and MRV, in combination with transferrin saturation (TSAT) for determining the responsiveness to the erythropoietin therapy.