The inventors have discovered that both soluble erythropoietin-binding protein and antibodies against the erythropoietin-binding protein, when they are administered to a mammal along with erythropoietin (Epo), prevent or reduce the blood pressure increase normally caused by erythropoietin, while not affecting the hematocrit increase that is the purpose of Epo treatment. The invention provides a method of treating anemia in a mammal involving: administering erythropoietin (Epo) to the mammal and administering to the mammal an agent selected from a soluble Epo-binding protein (Epo-bp), a recognition protein that binds Epo receptor on an extracellular soluble portion of the Epo receptor, and a combination thereof. The invention also provides a method of reducing hypertension in a mammal receiving Epo, and pharmaceutical compositions containing a soluble Epo-bp and/or a recognition protein that binds Epo receptor on an extracellular soluble portion of the Epo receptor.
