The effects of cyclophosphamide on hematopoietic stem cells (HSC) and on hematopoiesis was studied. Administration of 5 mg of cyclophosphamide to mice resulted in a rapid decrease in the number of HSC in the leg and spleen. The exocolonizing potential of HSC in the spleen recovered and reached supranormal levels in 7 days. That of HSC in the legs recovered to pretreatment values after 15 days. The endocolonizing potential of HSC in the leg, however, recovered in less than 4 days. The peripheral blood counts all dropped to a fraction of normal except for the platelet count, which was affected to a minimal degree. We suggest that cyclophosphamide irreparably damages most of the body's HSC. Those remaining in the leg then proliferate rapidly and repopulate other sites. HSC cannot, however, accumulate in the leg for more than a week after cyclophosphamide administration. Erythropoiesis does not recover until after this occurs. Platelets are least affected because of their resistance to the effects of the drug and because of the ability of megakaryocytes to increase their output of platelets without requiring differentiation of HSC into their compartment.

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