Erythropoietic response to exogenously administered recombinant human erythropoietin (rHuEpo) was examined in If maintenance haemodialysis patients with iron overload (IO). All had required numerous blood transfusions earlier ( > f 2 units/year). Diagnosis of IO was established by high serum ferritin (SF) levels ( > f ,100 μg/l), high hepatic CT density ( > 70 Hounsfield units; HU) and excessive iron stores in bone marrow aspirate (grade 6). None of the patients had osteitis fibrosa cystica, aluminium intoxication, haemoglobinopathy or haemochromatosis alleles (HLA A3, B7 and B14). All patients responded to rHuEpo treatment (target haemoglobin level of 9-10 g/dl). None of the patients required iron supplementation or developed ‘functional anaemia’. During 30 ± 3 months of therapy, the initial maintenance dose of rHuEpo (103 ± 12 units/kg/week) and median SF levels (2,250 μg/l) fell (50 ± 8 units/kg/week and 1,060 μg/l, respectively) (p = 0.0003 and 0.0007). The initial and final rHuEpo doses correlated well with the respective SF levels (r = 0.89, p < 0.001). The maintenance dose of rHuEpo required for patients with IO at the start of the treatment period was significantly higher than that (50 ± 5 units/kg/week) required by a control group of patients with adequate iron stores (SF = 100-600 μg/l) who were matched for age, sex and frequency of previous blood transfusions (p = 0.002). The findings suggested that excessive IO caused relative resistance to erythropoiesis on exogenous administration of rHuEpo and that iron supplementation was not warranted during rHuEpo therapy in those patients.