To examine the influence of intra- and post-operative blood loss and operative trauma on erythropoietin (EPO) production we studied patients undergoing endoprothetic surgery of the hip. Immunoreactive plasma EPO was determined in ten patients (seven male, three female, aged 39–68 years), undergoing surgery for hip arthroplasty (n=8) or revision hip arthroplasty (n=2). EPO levels had already been determined during preoperative autologous deposit, thus allowing direct comparison between EPO response to blood loss alone and the response to blood loss and operative trauma. Perioperative blood loss amounted to 1720 (480–8100) ml (median, range). The hemoglobin concentration decreased from 12.4 (10.6–14.0) g/dl (median, range) before the operation to 10.0 (9.3–12.3) g/dl 2 h after the operation. Thereafter, the hemoglobin concentration increased slowly due to transfusion and erythropoiesis and was not significantly different (p<0.05) from the preoperative value on the seventh postoperative day. The EPO concentration was preoperatively 26 (11–28) mU/ml and increased 2 h after the end of the operation, reaching a peak of 64 (45–104) mU/ml at 24 h. This peak was followed by a plateau at lower, but still elevated levels. The EPO concentration remained significantly elevated above the preoperative value on the seventh postoperative day. Plasma EPO concentrations showed an adequate response to postoperative anemia compared with the time course after autologous donation. In the early postoperative phase, they do not seem to be appreciably influenced by the neuroendocrine response to trauma, by mediators of inflammation, or by the postoperative catabolic state. The slightly elevated EPO concentration in the late postoperative phase indicates that factors other than anemia may contribute to EPO production at this time.