OBJECTIVE: To investigate whether treatment of anemia of chronic disease (ACD) in patients with rheumatoid arthritis (RA) with recombinant human erythropoietin (rHu-Epo) in combination with intravenous (i.v.) iron influences health related quality of life (HRQoL) and clinical outcome including disease activity. METHODS: Thirty patients with ACD and RA were treated with 150 IU/kg rHu-Epo twice weekly for 12 weeks. As well, in case of functional iron deficiency 200 mg of iron-sucrose per week was given intravenously. Vitality and fatigue as dimensions of HRQoL were evaluated by the vitality subscale of the Short Form-36 (SF-36-VT) and the Multidimensional Assessment of Fatigue (MAF). Muscle strength was measured by the Muscle Strength Index. RESULTS: All 28 patients completing the study responded to treatment; 23/28 patients developed functional iron deficiency and received i.v. iron (mean absolute dose 710 +/- 560 mg). Average hemoglobin concentration increased from 10.7 +/- 1.1 to 13.2 +/- 1.0 g/dl after a mean treatment period of 8.7 +/- 2.3 weeks. Muscle strength increased from 43.5 +/- 11.2 to 49.1 +/- 12.9 and SF-36-VT from 28.2% +/- 14.3% to 47.1% +/- 20.8%. while fatigue decreased (MAF from 34.7 +/- 9.3 to 25.0 +/- 11.3). Among the disease activity variables the number of swollen/tender joints, erythrocyte sedimentation rate, Disease Activity Score, and RA Disease Activity Index improved significantly during treatment. CONCLUSION: Treatment of ACD in RA patients with rHu-Epo and i.v. iron is safe and effective in correction of anemia, increases muscle strength. improves vitality, and lowers fatigue. In addition we observed a reduction of disease activity.