The spleen is a significant organ within the reticuloendothelial system (RES), which is part of the immune system. The reticuloendothelial system consists of monocytes and macrophages, which are phagocytic cells, as well as the associated reticular connective tissue where the phagocytic cells reside, such as the spleen or lymph nodes.

Aside from immune functions, the spleen also destroys aged red cells and recycles iron.