For patients who donate blood for autologous use and undergo major orthopedic surgery, low basal hematocrit (Hct) is the major cause of allogeneic blood exposure. To determine whether recombinant human erythropoietin (rHuEPO) could increase autologous blood procurement and reduce allogeneic blood exposure, a prospective randomized study was conducted in 50 women undergoing total hip replacement who had basal Hct < 40 percent (0.40). Patients were randomly placed in three groups: those receiving placebo, those receiving 300 U of rHuEPO per kg, and those receiving 600 U of rHuEPO per kg every 3 to 4 days for 21 days. Oral iron (125-270 mg/day) was given; in the last 24 patients, 100 mg of iron saccharate was administered intravenously at each donation. At each visit, 350 mL of blood was collected if Hct was > or = 34 percent (0.34). Patients receiving rHuEPO donated a greater amount of blood for autologous use than did patients in the placebo group (4.5 +/- 1.1 vs. 2.8 +/- 0.6 units; p < 0.05) and received a significantly lower amount of allogeneic blood (1.2 +/- 1.4 vs. 0.4 +/- 0.8 units; p < 0.05). No difference between the effects of the two doses of rHuEPO was observed. Iron support was a critical factor in the efficacy of treatment. No untoward effects were observed. The rHuEPO emerged as a safe and effective treatment, with adequate iron support, by which to increase preoperative deposit of autologous blood and to reduce exposure to allogeneic blood for patients with low basal Hct.