In an earlier report1 on the changes in weights of various organs of mice following total-body irradiation at weekly intervals, attention was drawn to the unusual nature of the changes in the spleen. The weights of the other organs varied with dose in a relatively simple manner; those of the more radiosensitive organs could be described by a linear change in the logarithm of the weight against dose. The spleen, however, showed a more complicated response. Its weight declined after series of low dosages but it became progressively heavier at the higher dose levels. We were able to show that this response was a summation of the changes in various cellular elements. The lymphoid follicles and the normal red pulp decreased in mass as dosage increased in the same manner as the radiosensitive organs, while areas of extramedullary myelopoiesis increased strikingly, from about 10 per cent of the splenic mass in controls to over 90 per cent following the highest dosage (six exposures to 200 r). When the latter areas were increasing rapidly, it was noted grossly (although not so obvious in sections examined under the microscope) that numerous nodules of regenerating tissue were visible on the splenic cortex. These areas were active mitotically and were composed of primitive hematopoietic cells. A preliminary study was therefore carried out of the course of similar regenerative phenomena in the spleens of mice given single totalbody radiation.2 As in the case of periodic irradiations, the splenic hyperplasia took place earlier (12-17 days after irradiation) and was more extensive following larger doses. In general, nodules appeared to be fewer and were rapidly growing at the higher dose levels. The maximum dose employed (550 r) represents something less than a 30-day LDls in this strain.