The pluripotential stem cell (CFU) compartment of marrow and spleen was evaluated in mice subjected to an intense erythroid stimulus associated with phenylhydrazine-induced anemia. Erythroid hyperplasia occurred in both marrow and spleen. CFU in the marrow gradually declined to approximately 50 per cent of control levels (day 5) while their numbers in the spleen increased (fourfold) by day 3 and were maintained at this level for several days. These changes in numbers of marrow and splenic CFU were not associated with CFU proliferation. Thereafter, CFU in the marrow, but not in the spleen, entered active cell cycle. The data suggest that CFU migrate from marrow to spleen during the demands of severe anemia. The induction of marrow CFU into cycle further suggests a negative feedback, which, perhaps through cell-cell interaction, maintains stem cells at a critical compartment size. The failure of splenic CFU to cycle may reflect the converse effect, i.e. an inhibition on stem cell proliferation in the wake of an expanded stem cell pool.