The administration of erythropoietin (EPO) can be used to increase a patient's hematocrit (Hct) in the preoperative period and thus possibly preclude the need for allogeneic red cells. However, the exact effect on the postoperative Hct of a given rise in Hct in the preoperative period (and on the avoidance of allogeneic blood) has not been thoroughly evaluated. Equations were developed on the basis of previously described relationships that allowed the assessment of the impact of a given preoperative Hct increase on the postoperative Hct under a variety of clinical situations. Equations were derived that related the change in preoperative Hct after the administration of EPO to the final Hct after a given blood loss. In a typical example (blood volume = 5000 mL, pre-EPO Hct of 40%, post-EPO Hct of 45% after blood losses of 1000, 2000, 3000, 4000, 5000, and 6000 mL), an additional 205, 168, 137, 112, 92, and 75 mL of red cells, respectively, would be present postoperatively over the volume in the same patient who did not receive EPO. For a smaller patient, such as a child (blood volume, 2500 mL), an additional 17 mL (5000-mL blood loss) to 83 mL (1000-mL blood loss) of red cells would be present postoperatively. Hemodilution and EPO act synergistically to yield additional postoperative red cell volume. The use of preoperative EPO with a preoperative increase in Hct results in an increased postoperative Hct after a surgical blood loss. Such a postoperative increase is a function of the volume of blood lost and the patient's blood volume but is independent of the patient's initial Hct. The final postoperative red cell volume increase associated with a preoperative increase in Hct of 1 to 5 percent is limited, however (generally equivalent to a fraction of 1 unit of allogeneic blood). Much of the increase in the patient's Hct vanishes at higher blood losses, and this therapy is most effective with blood loss of <4000 mL. EPO therapy alone may be most effectively used in patients with mild anemia who are undergoing routine surgical procedures that commonly require blood transfusion.