Various studies suggest that humoral substances, capable of stimulating CFU-S proliferation, are released into the plasma in response to depletion of the CFU-S population by cytotoxic substances such as cyclophosphamide. To test this hypothesis, we placed 0.25 ml of a murine marrow cell suspension with an equal volume of plasma from either normal mice or from mice previously injected with 5 mg of cyclophosphamide into cellulose dialysis tubing. These tubes were then incubated in the peritoneal cavity of mice for 1–7 days. The CFU-S content of the tubes was then assayed. The CFu-S content of suspensions in normal mouse plasma declined to one-fourth of the initial value after 7 days, whereas those in plasma from mice that received cyclophosphamide 7 days previously were essentially unchanged in number. These data suggest that 7 days after injection of cyclophosphamide, the plasma contains a factor that either prevents death of CFU-S or stimulates them to proliferate. An alternative explanation is that normal plasma contains an inhibitor of CFU-S growth that is lacking in plasma of cyclophosphamide-treated mice.