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The erythropoietic effect of 5beta-pregnane-3beta-hydroxy-20-one, a naturally occurring steroid metabolite of progesterone, was evaluated in the squirrel monkey by ferrokinetic studies. red cell survival, and blood volume measurements. The intramuscular administration of this steroid in pharmacologic doses shortened the (59)Fe plasma clearance and increased the plasma iron turnover, thereby indicating an increase in erythropoiesis. A normal (59)Fe red cell uptake was observed, and the bone marrow maturation time was not altered. Red cell survival was the same in the treated and control groups. After five weekly injections of the steroid, the monkeys increased their red cell mass by 57%. A significant increase in white blood cells and a slight elevation of platelet counts in the treated monkeys also suggest a possible direct stimulation of hemopoietic stem cells by the steroid metabolite. These observations indicate that some steroid metabolites can stimulate an early increase in iron turnover (within 48 h) that is not secondary to hemolysis. The increased red cell mass indicates effective erythropoiesis in primates.