Abstract X-irradiation with a shielded leg markedly increased the endogenous colonizing potential of cells in the shielded leg. This effect reached its peak magnitude 7 days after x-irradiation. The number of transplantable colonies in the shielded leg was unaltered. The reasons for differences in the endocolonizing and exocolonizing potentials of cells were investigated and discussed. We concluded that that the ability of colony forming units in an unirradiated site to respond to depletion of those elsewhere suggests that hematopoietic stem cells are probably regulated by a humoral factor.