Patients receiving recombinant human erythropoietin (rHuEPO) therapy show wide variability in their responsiveness to the drug. Variables that affect rHuEPO dose requirements can be broadly divided into modificable and immutable characteristics. Most of the scientific research on rHuEPO hyporesponsiveness has focused on modificable variables (iron status, dialysis adequacy), while immutable variables such as gender, etiology of chronic renal failure (CRF) and age have been insufficiently explored. A cross sectional study was performed in order to evaluate if immutable patient characteristics determine rHuEPO dose requirements among 215 patients (52% males; mean age 66 +/- 14 years) on hemodialysis (HD) for more than twelve months. Data were collected at 10 hemodialysis units in Aragon. Patients were divided into three groups according to their gender, their cause of CRF (diabetic nephropathy, vascular nephropathy, tubulointerstitial nephropathy and primary glomerulonephritis) and their age (younger than 60 years, from 60 to 75 years, older than 75 years). Despite a similar dose of rHuEPO, women had lower mean hemoglobin (11.1 +/- 1.5 versus 11.6 +/- 1.7 g/dl; p = 0.0258) than men. The greater hemoglobin in men than women may be attributed to greater serum albumin in men (3.5 +/- 0.3 versus 3.7 +/- 0.3 mg/dl; p = 0.0001). Requirements of rHuEPO were higher in the patients with etiology of primary glomerulonephritis compared with those with the other etiologies, even those with diabetic nephropathy (p = 0.0374). The rHuE-PO doses required to obtain similar hemoglobin levels were higher in patients younger than 60 years (p = 0.0249). We conclude that women, patients with primary glomerulonephritis as cause of CRF, and patients younger than 60 years showed the highest requirements of rHuEPO doses.