We treated 5 patients with rheumatoid arthritis (RA) with anemia of chronic disease with recombinant human erythropoietin (rHuEPO) for 11 weeks. An increase in hematocrit (Hct) greater than 5 was seen in 4 patients after 4 weeks of therapy. The 5th patient had a significant rise in Hct when the dosage of rHuEPO was increased to 150 units/kg from the 4th to 7th week. The subcutaneous administration of rHuEPO dose, reduced by one third with respect to initial dose, maintained an effective Hct value in all the 5 patients during the last 4 weeks of therapy. There was no change in disease activity. In one patient Hct normalization completely resolved symptoms of angina pectoris and permitted hip replacement surgery in another. No side effects occurred during rHuEPO therapy. We conclude that HuEPO is an effective, safe and well tolerated therapy for RA patients with severe anemia of chronic disease.