The effect of an androgen, 19-nortestosterone decanoate (19-ND), on radioironincorporation into peripheral red blood cells wastested in the plethoric (PCT) and the plethorichyperoxic(PCT-HOX) mouse. When 19-ND wasinjected 24 hr prior to the administration of exogenouserythropoietin (ESF), it was observedthat these mice responded with significantlygreater levels of erythropoiesis, as measured by50Fe incorporation into peripheral red blood cells,as compared to identical mice injected with ESFalone. Additional observations showed that hyperoxia(HOX) was capable of significantly decreasingthe already minimal levels of erythropoiesisnormally found in PCT mice and that this PCTHOXanimal did not respond as markedly toandrogen therapy as the PCT animal. The additionof assayable minimal amount of ESF didnot cause further augmentation of radioiron incorporationin the groups receiving ESF only.Since plasma ESF activity was not found to beelevated to detectable levels following androgenadministration in PCT-HOX mice, it was concludedthat these studies are compatible with theconcept that the androgen increased the size ofa stem cell population capable of responding toESF and that further differentiation of these elementsrequired the presence of ESF. (Endocrinology93: 777, 1973)