Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels. It prompts the production of erythrocytes. Some athletes use synthetic EPO as a performance-enhancing drug (called blood doping) to increase RBC counts and subsequently increase oxygen delivery to tissues throughout the body. EPO is a banned substance in most organized sports, but it is also used medically in the treatment of certain anemia, specifically those triggered by certain types of cancer, and other disorders in which increased erythrocyte counts and oxygen levels are desirable.

EPO is a hormone that is critical to our overall vitality. Produced in the kidneys, EPO travels through the bloodstream and enters the marrow of certain bones through their porous exterior. There, it binds to stem cell surface receptors and instructs the developing cells to become red blood cells.

Most EPO production takes place in the renal cortex, in the upper portion of your kidneys. EPO production is stimulated when oxygen levels in the renal vasculature (blood vessels) drop. EPO travels from your kidneys to your bone marrow, where it binds to receptors in the walls of stem cells. This triggers a series of events inside the stem cells that instructs their DNA to transform them into red blood cells.

Some people lack sufficient amounts of EPO. Fortunately, a synthetic version of EPO is available that can be taken through subcutaneous (under the skin) injection, several times a week. Longer-acting EPO may also be given intravenously every other week.

In its original intent, the term blood doping was used to describe the practice of injecting by transfusion supplemental RBCs into an individual, typically to enhance performance in a sport. Additional RBCs would deliver more oxygen to the tissues, providing extra aerobic capacity, clinically referred to as VO₂ max. The source of the cells was either from the recipient (autologous) or from a donor with compatible blood (homologous). This practice was aided by the well-developed techniques of harvesting, concentrating, and freezing of the RBCs that could be later thawed and injected, yet still retain their functionality. These practices are considered illegal in virtually all sports and run the risk of infection, significantly increasing the viscosity of the blood and the potential for transmission of blood-borne pathogens if the blood was collected from another individual.

With the development of synthetic EPO in the 1980s, it became possible to provide additional RBCs by artificially stimulating RBC production in the bone marrow. Originally developed to treat patients suffering from anemia, renal failure, or cancer treatment, large quantities of EPO can be generated by recombinant DNA technology. Synthetic EPO is injected under the skin and can increase hematocrit for many weeks. It may also induce polycythemia and raise hematocrit to 70 or greater. This increased viscosity raises the resistance of the blood and forces the heart to pump more powerfully; in extreme cases, it has resulted in death. Other drugs such as cobalt II chloride have been shown to increase natural EPO gene expression. Blood doping has become problematic in many sports, especially cycling. Lance Armstrong, winner of seven Tour de France and many other cycling titles, was stripped of his victories and admitted to blood doping in 2013.