A prospective study with 65 maintenance hemodialysis (MHD) patients on recombinant human erythropoietin (rHuEPO) therapy was conducted to assess the effect of iron balance on responsiveness. An attempt to define the predictors of erythropoietin (EPO) response and identify the specific causes of EPO resistance was undertaken in the present study. The treatment protocol consisted of two stages, the first was rHuEPO therapy for 6 months and the second was iron supplementation plus rHuEPO therapy in patients without response to EPO for the next 6 months. According to the hemoglobin (Hb) changes (increment exceeded 30% of baseline or did not exceed 15% of baseline for 3 consecutive months) and whether or not there was an achievement of target Hb level (>10.5 g/dl), all patients (n = 65) were divided into EPO-responsive (n = 20) and EPO-resistant (n = 45) groups. The EPO-resistant patients were then further stratified into iron-responsive (n = 29) and iron-irresponsive (n=16) groups. Iron metabolism and red cell indices were analyzed prior to and following rHuEPO therapy and iron supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)