A consistent deficit in the red cell mass has been observed during both the American and Soviet orbital space flights and is sometimes referred to as “astronaut anemia.” This may be associated with a reduction in plasma volume so that the hematocrit and the hemoglobin concentration remain unchanged. During the Gemini program, the hypobaric hyperoxic atmosphere of the spacecraft led to oxidative injury to the red cells, causing hemolysis. Thus, the atmosphere proved to be, in part, responsible for the deficit. However, a similar deficit of a lesser magnitude was again observed in subsequent flights with normal ambient PO2 as well as in the Soviet flights in which an atmosphere essentially of see level air is used. The cause of this deficit seems to be suppression of erythropoiesis, as indicated by reticulocytopenia and erythroid hypoplasia of the marrow. No suppression of erythropoiesis has been observed in ground-based experiments carried out under almost identical conditions. Thus, the suppression of erythropoiesis is thought to be related to weightlessness. The reason for the suppression is not known but may be related to total inhibition of bone formation.