OBJECTIVE Rheumatoid arthritis (RA) is generally associated with mild anaemia. The role of erythropoietin (EPO) in the pathogenesis of this anaemia of chronic disorders is still a matter of controversy. Therefore, in a multicenter study we investigated the serum EPO concentration in 124 patients with rheumatoid arthritis. METHODS Patients with uncomplicated iron deficiency and haemolytic anaemia served as the reference group (n = 54). The measurements were performed with a specific and sensitive ELISA: RESULTS The mean EPO concentration +/- SD of the whole RA group (32.3 +/- 22.2 mU/ml) was elevated above normal. About 40% of the patients had underlying iron deficiency (defined by ferritin values < or = 60 ng/ml) and a significantly higher median EPO concentration than patients with normal iron stores (35.8 mU/ml versus 20.7 mU/ml; p < 0.001). The iron deficiency was associated with lower disease activity, as defined by the C reactive protein. In contrast to the reference group (r = -0.78), there was no significant correlation between EPO and the haematocrit in either RA subgroup, although the values for the RA patients were within the 95% prediction range of the reference group. In addition to the EPO, we investigated the soluble transferrin receptor level as a measure of bone marrow erythropoiesis. The level in iron-replete RA subjects was about 1.6 times higher than in normal persons, reflecting a relatively hypoproliferative erythropoietic activity. CONCLUSIONS This study shows that the EPO concentrations in RA are elevated above normal but lower than expected, and that the normal relationship between EPO and the degree of anaemia is impaired.