Iron metabolism was studied in 21 patients with the anaemia of end-stage renal disease during 40 weeks of treatment with recombinant human erythropoietin (rhEPO). Oral iron was prescribed to all patients. Initial serum iron concentrations and transferrin saturation levels were subnormal, decreased during the correction period of treatment, and increased thereafter. In 81% of patients in whom pretreatment transferrin saturation was below 0.25, transferrin saturation decreased below 0.16, despite sufficiently high serum ferritin levels. Serum ferritin concentrations decreased significantly. There was no correlation between serum ferritin levels and serum iron or transferrin saturation. Ferrokinetic studies, performed before and during treatment, showed an increase in plasma iron turnover, in erythron transferrin uptake, and in the flux of iron binding sites through the plasma. The rhEPO dose needed to keep the haematocrit at the target level during the maintenance period of treatment was significantly correlated with transferrin saturation, and iron binding capacity, but not with serum ferritin concentrations. This suggests that the functional availability of iron in plasma, rather than the size of body iron stores, is a major factor in the determination of the response to rhEPO treatment in end-stage renal disease.