Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation. The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections. Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma. The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected. Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.