The effect of prolonged hypoxia on the mouse hemopoietic system has been examined in order to ascertain the effect of this intense stimulus on quantitative measures of differentiation and proliferation on the erythropoietic system.

The first change that was observed (2-3 days after hypoxia) was a marked increase in the in vitro iron incorporation of the spleen cells and a less marked increase of that of the marrow cells. Later (at 4 days), there was an increase in peripheral reticulocytes. Following both of these events there was a marked decrease in the number of colony-forming cells in the spleen of the hypoxic mice but no change in the number in the marrow.

We conclude that the primitive erythroid precursor that is sensitive to erythropoietic stimulation is not the colony-forming cell. We suggest, instead, that the late decrease in colony-forming cells in the spleen is a response to a depleted pool of cells sensitive to erythropoietin and that colony-forming cells are differentiated to produce more of these cells.

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