Erythropoietic stem cell damage and recovery after treatment with radio-protective agents followed by gamma irradiation was measured in transfusion-induced polycythemic mice in conjunction with 59 Fe red cell incorporation as the indicator of erythropoietic activity. In irradiated mice, the administration of S-2 aminoethylisothioureadihydrobromide (AET) prior to irradiation results in less initial damage to the blood and spleen, and this is responsible for the earlier recovery of the erythropoietic system. Blood and spleen 59 Fe values at 1 or 7 days after irradiation with 200 or 700 rads, respectively, can be used to compare the relative value of different sulfhydryl agents in aiding survival. Using the split-dose technique, it was shown that AET given prior to the second radiation dose provided protection to the hematopoietic system and increased survival. However, AET prior to the first radiation dose (200 rads) did not produce any increased protective effect over that produced by the first radiation dose when the mice were irradiated 10 days later.