The anemia of multiple myeloma (MM) is multifactorial, including physical replacement of normal hemopoiesis by tumor cells, renal failure and cytokines which contribute to the blunted erythropoietin (EPO) response observed in anemias of chronic disease. Recombinant EPO has been evaluated in anemic patients with stable multiple myeloma (≤10g% hemoglobin). Responses (≥2g% hemoglobin increase) were observed in 78% of 41 patients in two separate studies. Responses were associated with an increase in bone marrow erythropoietic cell compartment and reticulocy tosis. Evaluation of potential parameters affecting response identified prolonged cyto-toxic therapy for >12 months, especially with alkylating agents and pre-treatment EPO levels >100 U/L, both of which seemed to decrease the likelihood of EPO response. EPO is a safe and effective treatment for the anemia associated with MM.