The human spleen, an organ of unique anatomic and functional importance, is the largest component of the reticuloendothelial system, with direct interposition between systemic and portal circulation, and yet the morphologic correlates of its various functions remain somewhat mysterious. The contributions of transmission and scanning electron microscopy to the understanding of splenic structure have been considerable. They have helped clarify the three fundamental sites of structural alteration and specialization that are defined and discussed: 1) the white pulp with its two variable components--the lymphoid follicle and periarteriolar sheath--which, with the marginal zone of the red pulp, is the primary site of lymphoproliferative activity; 2) the cords of the red pulp, the functionally slow component of the splenic circulation, which sequester senescent or structurally altered red cells and effect their removal by means of scavenging macrophages (and which may be secondarily involved by the accumulation of platelets or certain types of leukemic cells, resulting in chronic cordal distention, or by the accumulation of collagen in fibrocongestive splenomegaly); and 3) the splenic sinuses, the unique structure of which determines that only healthy red cells with normally plastic and flexible membranes pass through to the venous circulation. Abnormal transiting cells such as sickle cells frequently clog the apertures to these sinuses. Direct arteriocapillary sinus terminations provide the anatomic basis for a fast component of the red pulp circulation, the existence of which was questioned for many years and the extent of which is still unknown in pathologic states.