Thermal injury is associated with an anemia of multifactorial etiology. Erythropoietin is a hormone that increases red blood cell production in response to tissue hypoxia and is now being produced in a recombinant form for treatment of some anemias. How erythropoietin levels change in response to thermal injury has not been adequately investigated to date. We studied 27 patients with burns of 10% to 85% total body surface area by serially measuring hemoglobin, hematocrit, reticulocyte count, and erythropoietin levels. Erythropoietin levels were determined by radioimmunoassay. Measurements were taken at admission, before surgery, and after surgery, or at least weekly for a period of up to 4 weeks. Twenty-five of the patients had a reticulocytopenic anemia by the end of the first postburn week. Twenty-three patients remained anemic throughout the study period. Erythropoietin levels increased appropriately as the patients became anemic. Erythropoietin levels related to hemoglobin in a logarithmic fashion with a correlation of -0.869. No differences were found on the basis of burn size or age. This study indicates that the anemia of thermal injury is associated with reticulocytopenia and an elevation of endogenous erythropoietin.