Abstract We studied whether orthopedic surgical patients with rheumatoid arthritis (RA) can generate an erythropoietic response to either endogenous erythropoietin or to recombinant human erythropoietin (EPO) therapy to the same extent as patients without rheumatoid arthritis (non-RA). Seventy patients (10 RA, 60 non-RA) were entered into clinical trials of aggressive autologous blood donation before elective orthopedic surgery at one institution, randomized to receive EPO (600 U/kg, iv, 6 times over 3 weeks) or placebo. RA patients given EPO had red blood cell (RBC) production that was enhanced by 624 ± 137 ml (mean ± SD) as compared with 271 ± 174 ml ( p = 0.02) for RA patients given placebo treatment. Preoperative RBC volume expansion in 10 RA patients was 5.9 ± 3.7 ml/kg as compared with 7.4 ± 3.9 ml/kg for 60 non-RA patients ( p = 0.13). RA patients can benefit to the same extent as non-RA patients from aggressive blood conservation programs that incorporate erythropoietin-modulated erythropoiesis.