Preliminary studies have indicated that plasma levels of erythropoiesis-stimulating factor (ESF) increase in mice after irradiation and hypoxia. ESF production was therefore studied in five groups of female B6 C3 F1 mice. (1) Exposure of mice to hypoxia (approx. 7% O2) by enclosure in silicone rubber membrane cages resulted in ESF levels of about 2.5 units of ESF per milliliter of plasma at 24 hours. The circulating ESF levels then decreased to less than 1 unit/ml as the hematocrit values increased. (2) Mice subjected to 450, 750, 950, and 1200 R of x-rays and kept at normal O2 levels had undetectable amounts of ESF until day 8. After 950 R ESF levels then rose sharply as hematocrits decreased, and on day 10 the mice produced about 4 units of ESF/ml of plasma. (3) In experiments in which mice were exposed to x-rays and hypoxia, distinct cyclic elevations of ESF activity were observed. (4) Mice given bone marrow transplants (injection of 1, 5, and 15× 106 homologous bone marrow cells) after irradiation did not show the characteristic increase in ESF levels by day 10. (5) However, markedly increased levels of ESF with obvious cyclic elevations were observed in mice enclosed in membrane cages after irradiation and bone marrow transplantation. These data indicate that transplantation of small numbers of bone marrow cells markedly alters the pattern of ESF elaboration after otherwise lethal doses of x-ray.

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