Employing the erythroid colony-forming technique, it is shown that throughout hepatic erythropoiesis in the mouse, the CFU-E population remains sensitive to erythropoietin. Maximum stimulation was achieved during this period using an erythropoietin concentration of 0075 units/ml. The peak in the CFU-E concentration occurs between the 11th and 12th day while absolute values show a maximum on the 14th day of gestation. These results are discussed in terms of changing cell populations, both of erythropoietic precursors and hepatocytes from which it is concluded that at no time during foetal erythropoiesis does the CFU-E population change or become unresponsive to erythropoietin. The BFU-E population follows closely that of the CFU-E, but declines about 24 h earlier on the 16th day of gestation. The effect of the foetus on the mother was also studied during the second half of pregnancy. During this period of natural perturbation both femoral and, in particular, splenic erythropoiesis are increased. However, during this time an erythropoietin concentration of 0-3 units/ml was required to maximally stimulate the CFU-E population derived from these tissues. The fact that both adult and foetal erythroid tissue maintain a rather constant requirement for erythropoietin for their growth in vitro, indicates that it is an intrinsic property of the cells. It is concluded that increased maternal erythropoiesis is due to an increased oxygen requirement causing hypoxia due to the growing foetus.