Erythropoietin (ESF) levels were assayed in rats bearing the Wistar-Furth Wilms' transplantable tumor. Sites of tumor inoculation varied from subcutaneous, intramuscular, intrarenal (subcapsular), to intraperitoneal. Two-thirds of the animals exhibited ESF elevations without polycythemia, or severe anemia (HCT less than 30.0 vol%). The elevations of ESF were not detectably related to the time of sacrifice (age of the animal), size of the primary tumor, or number of gross metastatic foci. The diminished ESF response noted to animals given intramuscular tumor implantations is believed to reflect differences in tumor blood and lymphatic supply at the various sites of inoculation. The pattern of ESF responses in the Wistar-Furth Wilms' tumor model is thus quite similar to that which we have observed in man, and appears to represent an animal model for tumor-related ectopic hormone release. The nature of the hormone is believed to differ from that seen in normal physiological states.