Fe59 turnover was studied in normal and lethally irradiated rats with and without intravenous bone-marrow treatment. An intensified activity in both the spleen and bone marrow was maintained up to 2 months after irradiation. Development of this activity proceeded at about the same pace in both organs and they maintained nearly the same relative activity as in normal unirradiated animals. These findings are in contrast to the biphasic pattern of erythropoietic recovery in the rat after sub-lethal whole body irradiation with or without hind-limb shielding. Under such conditions, the recovery of splenic erythropoiesis preceded that of the irradiated bone marrow, though an abortive erythropoietic activity occurred in the unshielded limb. Even in a rat strain in which no splenic erythropoiesis was normally found, erythropoietic activity developed after irradiation with or without hind-limb shielding as well as after intra-peritoneal injection of bone-marrow homogenate. In a lethally irradiated untreated group studied 7 days after irradiation, the Fe/sup 59/ distribution curves suggest the occurrence of a slight degree of erythropoietic recovery shown by a higher Fe/sup 59/ bone-marrow curve, a slight increase in the circulating labelled red cells, and some degree of mobilization of the hepatic Fe59. The bone-marrow curve showed a highermore » peak compared with the corresponding curve at 4 days, but the subsequent release of Fe59 was very slow. This would be explalned either by a relative deficiency of late forms of red-cell precursors which are very radiosensitive or by a lag in the maturation and release of these late forms. The data indicate that the therapeutic effect of bone-marrow transplantation was simply the provision of a greater number of functioning erythropoietic cells in the normal sites than in the intact animal. This would enhance erythropoietic recovery without any localization in ectopic sites, and no ectopic foci of erythropoiesis were demonstrated.« less