The importance of the spleen to recovery of lethally x-irradiated mice injected with syngeneic bone marrow was evaluated. When splenectomy was performed 2 days before irradiation, injection of marrow resulted in 30-day survival, which was the same as that of intact mice. However, when splenectomy was performed 2 or 3 days after exposure and marrow injection, survival was decreased, probably because the fraction of marrow committed to the spleen was removed. Results of ferrokinetic studies (⁵⁹ Fe) showed that early regenerative erythropoiesis in lethally irradiated mice injected with marrow is reduced in animals splenectomized before irradiation, but only when the marrow cell dose is limiting. Even at a limiting cell dose, erythropoiesis is eventually restored to that of intact mice. Thus the spleen appears to contribute to early restitution of a hemopoietic compartment least critical to survival of the animal, and whatever contribution the spleen makes to survival is compensated by other tissues when the spleen is absent. Interpretation of splenic contribution to hemopoietic regeneration and survival is complicated by the fact that splenectomy performed 2 days before irradiation increases the about 65 R. This kind of protective effect, however, is also manifested by uninephrectomy but not by partial hepatectomy or uniorchidectomy. Our data shed no light on the basis for this kind of radioprotection.