The radiation syndrome that kills mice in 3.5 days was found to be mainly due to irradiation of the small intestine. Radiation injuries were defined by anatomical fractionation following irradiation first of the entire body region, then of smaller areas, and finally of surgically exposed individual organs. Irradiation with 1200 rad or more of any region that includes the entire small intestine resulted in death at precisely the same time as irradiation of the whole body. Irradiation of any major fraction of the bowel alone resulted in death under the same circumstances but at a slightly later time, and irradiation of the entire body minus the protected surgically exposed small intestine did not cause a comparable syndrome. The sequence of histological changes in the intestinal epithelium after irradiation is described and cell population kinetics in the irradiated animal is discussed. (C.H.)