Experiments were performed to determined the effect of protein deprivation on CFU-S in the spleen and femoral marrow, on the peripheral blood counts, and on the rate at which these parameters regenerate following radiation. Splenic CFU-S decrease in number after only 3 days on diets containing 5% protein or less. Marrow CFU-S, on the other hand, decrease only after mice are fed a protein-free diet for 4 weeks or more. The hematocrits, platelet counts, and WBC counts fall in the latter group. Marrow CFU-S regenerate more slowly in irradiated mice fed diets containing 5% protein or less. Also, the hemocrits, WBC counts, and platelet counts of irradiated mice fed diets containing 5% protein regenerate more slowly than do those of irradiated mice fed normal diets. The effect of protein deprivation on erythropoietin production, erythropoiesis, granulocyte function, and immunocompetence is well known. The studies reported here indicate, in addition, that protein deprivation also causes the numbers of CFU-S and the platelet counts to decline.