DOSE INCREMENT and patterns of dose fractionation are often modified in clinical radiotherapy, depending upon the response and tolerance of the patient. Small changes in daily dose rate may result in obvious clinical differences. This is most apparent in the region of the head and neck, where the response of the mucosal tissues is easily observed. The purpose of this study is to quantitatively explore some current fractionation schemes and their modifications as applied to an in vivo system during differing proliferative states. A preliminary description of some of these data has been reported previously (3). An in vivo assay system developed by Till and McCulloch (9) was used to compare different clinical dose fractionation schemes. Mice were subjected to whole-body radiation of 500 to 900 R, and macro-scopic spleen colonies (endocolonies) were noted nine days later. Similar colonies can be formed by injecting syngeneic bone marrow intravenously into animals which have previously been irradiated sufficiently to prevent the proliferation of endogenous colonies (8). These “exocolonies,” composed of proliferating and maturing erythrocytic, granulocytic, and thrombocytic elements, appear to be derived from a single cell (2). Compared to exocolonies, endocolonies have the advantage of affording a means of assessing the population in situ without the manipulation of transplantation. However, endocolonies also suffer from the disadvantage of being more variable in size and hence more difficult to count. Colony-forming cells normally exist in a steady state with a relatively low rate of turnover, but they respond to transplantation into irradiated recipients by greatly increasing their proliferative rate (1). Thus these systems allow study of hemato-poietic colony-forming cells under two different proliferative states: slow proliferation prior to irradiation in the endocolony assay, and rapid proliferation in the exocolony method. Using these different kinetic systems, the effects of variations in fraction size, interval between fractions, and change in fractionation pattern are investigated. Methods Male C3H mice2 were used in all experiments. Most animals were from three to six months old, although a few were older. The mice were randomly allocated to experimental groups. X-radiation factors in all experiments were 250 kVp, 15mA, h.v.I. 1.65 mm Cu, SSD 50 ern, and output 114 R/minute. Dose rate was measured with a Victoreen chamber in a mouse phantom. Groups of animals were given whole-body irradiation while on a rotating turntable in a 10-cell cage. Animals were housed 5 per cage and given food and water ad libitum. Endocolony Technic: Experimental and control groups containing 15 and 20 mice were irradiated as described above.