Therapy with recombinant human erythropoietin (rEPO) can correct anemia in RDT patients. However, iron deficiency can develop making treatment unsuccessful. Eighteen non-transfused RDT patients with hematocrit less than 26% were treated with rEPO to raise the HCT to 30-35%; then the dose was individually adjusted to maintain the HCT. The mean HCT rose from 22.3% to 31.5%. Ten patients received iron substitution before rEPO. During rEPO therapy five further patients had to be supplemented with iron; all patients needed an increase in the oral iron doses and three required i.v. iron. During the correction phase mean serum ferritin dropped from 203 micrograms/l to a minimum of 71 micrograms/l and was 102 micrograms/l after six months. Serum iron and TIBC changed only moderately. It thus appears that iron demand rises markedly during rEPO therapy, requiring iron substitution in most patients. Serum ferritin is the most sensitive parameter for development of iron deficiency.