Inadequate iron supply is probably the most common and most easily treated cause of sub-optimal response to recombinant human erythropoietin (r-HuEPO). A low ferritin value is a reliable indicator of iron deficiency, provided that patients are in equilibrium (e.g. without infection, bleeding, vitamin or folate deficiency). Normal or high ferritin values do not necessarily preclude iron deficiency. Transferrin saturation is not always a reliable indicator of iron deficiency. The measure which best reflects iron supply to the erythron is the percentage of hypochromic red cells. Iron supplementation should be targeted at keeping serum ferritin > 100 mu g/l, transferrin saturation > 20%;,, and hypochromic red cells < 10%, Iron status should be monitored monthly for the first few months after initiation of r-HuEPO, and thereafter at 2-3 month intervals. For haemodialysis patients, who have a very high rate of iron loss, i.v. iron administration is preferable and may also be appropriate for patients on continuous ambulatory haemodialysis (CAPD) and pre-dialysis patients. Recent studies with i.v. iron supplementation have shown no difference between the s.c. and i.v. routes of administration of r-HuEPO. Both the i.v. and the s,c. route are appropriate for patients on haemodialysis, whereas patients on CAPD or pre-dialysis patients should receive s.c. r-HuEPO. The optimum frequency of s.c. administration in the vast majority of patients is 2-3 times weekly. For a small number of patients, once weekly s,c. administration may be suitable. When satisfactory haemoglobin values are reached, the dose of r-HuEPO should be titrated down gradually. It should not be stopped abruptly unless there are life-threatening complications.