A general review showing that the mammalian spleen, while not necessary for the maintenance of normal existence and sharing many of its functions with other members of the hemolyto-poietic system, is useful in several ways and an organ whose presence under certain stresses may even be the deciding factor between life and death. Its functions are largely indicated by its structure, its reticulo-endothelial cell content and by the changes produced in other organs by its absence. There is good reason to consider it a blood reservoir that can be called upon efficiently to meet various physiological and pathological demands. It is directly concerned in blood cell formation during fetal life and can revert to this function upon demand at any period of existence. It continues to furnish lymphocytes, large mononuclears and possibly other blood cells through most of the adult life and has an indirect influence on blood formation, through a stimulating action on the bone marrow, possibly after activation by the liver. It is intimately concerned in the processes of red blood cell destruction, a role greatly increased in certain pathological conditions. It not only, in some way as yet unknown, renders circulating erythrocytes more fragile, but through its reticulo-endothelial cells, has the ability to scavenge blood cells and bacteria from the blood. It takes up disintegrating erythrocytes as a step in blood pigment metabolism, either in the form of fragmented cells, hemoglobin bearing dust, or even[long dash]in conditions of increased hemolysis[long dash]of whole cells (graveyard function). It not only is the richest hoarder of iron in the body, but also prepares bilirubin pigment from the broken down hemoglobin for passage to the liver. In the absence of the spleen it becomes more difficult to produce jaundice with hemolytic agents. Continental authorities consider it the controlling organ of iron metabolism in the body. It seems to be an important site of antibody formation (again through the reticulo-endothelial cells), though this function is quickly taken up by other organs in its absence. Through its lymphoid role, it also plays a part in resistance to such infections as tuberculosis. Preponderating evidence points to its also being concerned with biological resistance to tumor growth. Its relation to metabolism (growth and digestion, basal, nitrogen and carbohydrate metabolism) is also manifest. With regard to its relations to other organs, the liver, lymph nodes (lymphoid tissue generally) and bone marrow, as members of the hemolyto-poietic system, are so closely allied that they share certain of its functions normally and quickly take over the remaining share after extirpation of the spleen. It has special affiliations with the liver on account of its definite "upstream" position in the portal circulation and possibly others of a more specific incretory nature.