AbstractErythropoietin (ESF) levels were assayed in 19 female and male patients with intact kidneys with pituitary tumors or following open hypophysectomy or combined hypophysectomy and adrenalectomy for disseminated tumor states. Saline‐injected control mice had 0.38 ± 0.04% Fe59uptake (ESF). Hypophysectomized, adrenalectomized, castrated females had 2.96 ± 1.24% Fe59uptake (ESF) with an average peripheral hematocrit of 29.2 vol %. Hypophysectomized, castrated males had 1.59 ± 0.30% Fe59uptake (ESF) with an average peripheral hematocrit of 30.1 vol %. Thus, absence of the adrenals or functioning anterior pituitary gland does not prevent increased ESF activity. The presence of a pituitary tumor is also not consistently associated with increased ESF activity or release. The role of these endocrine organs in the regulation of ESF release in these states is therefore not essential but more likely represents a normal synergistic mechanism. Elevation of peripheral ESF levels is associated with improvement of anemia after hypophysectomy and may be an additional objective criterion and prognostic indicator of beneficial patient response to hypophysectomy in certain tumor st