BJECTIVE: To evaluate the effectiveness of a stepwise use of recombinant human erythropoietin (rhEPO) in pregnant patients with severe anemia or nonresponsive to intravenously administered iron only. METHODS: All subjects had iron deficiency anemia, i.e., a hemoglobin (Hb) level <10.0 g/dl and ferritin < or =15 microg/l. Patients with an Hb level > or =9.0 g/dl and <10.0 g/dl received 200 mg iron sucrose intravenously twice weekly. If response to therapy was poor, patients additionally received 10,000 U rhEPO twice weekly. Patients with an Hb level <9.0 g/dl primarily received iron sucrose and rhEPO likewise. RESULTS: Of the 84 patients, 59 had a baseline Hb level between 9.0 and 9.9 g/dl, of whom 32 responded poorly, thus receiving additional rhEPO. Twenty-five patients had a baseline Hb level <9.0 g/dl. The overall Hb level after therapy was 11.0 g/dl (+/-0.5, range 10.0-12.6 g/dl). Mean duration of therapy was 3.5 weeks (7 infusions). CONCLUSION: This study shows an effective treatment regimen for patients with various degrees of anemia in pregnancy. Iron sucrose is a safe and effective treatment option. In cases of severe iron deficiency anemia or poor response to parenteral iron therapy additional administration of rhEPO might be considered. However, the mechanism for not responding to intravenous iron therapy despite iron deficiency anemia still remains unclear to a large extent.