Treatment of mouse hematopoietic cells with heterologous antiserum raised against mouse brain markedly reduces the capacity of pluripotent stem cells (CFU-S) to form surface spleen colonies in lethally irradiated mice. To exclude the possibility that such treatment interferes only with the capacity of CFU-S to form surface spleen colonies, we evaluated the capacity of CFU-S which were treated with rabbit anti-mouse brain serum (RAMBS) to restore hematopoiesis and rescue lethally irradiated mice, and to form microscopic spleen colonies. Marrow cells were treated with RAMBS or control rabbit serum. Fifty thousand treated nucleated cells were injected i.v. into lethally irradiated mice, and hematopoietic reconstitution was studied between days 8 and 15; separate groups of mice were observed for survival. We found that treatment with RAMBS impairs the capacity of marrow cells to repopulate the marrow and spleen with CFU-S, to restore blood RBC, to effect an overshoot in spleen weight, and to prolong survival; in addition it reduces the number of microscopic spleen colonies to the same extent that it reduces the number of macroscopic colonies. Hence, RAMBS appears to effect a general inactivation of CFU-S and should prove to be a useful tool in further investigations of mouse hematopoiesis.