Splenic microcorrosion casts prepared using minimal volumes of material show that most of the flow passes through the region bordering the white pulp. However, the nature of these microcirculatory pathways has received little attention. We have studied these in dog, cat, rat, mouse, and normal versus diseased human spleens. In all 5 species, a marginal sinus (MS) of anastomosing vascular spaces 5-10 microns thick lies between the white pulp and marginal zone (MZ). The morphology differs between species and the MS is absent in immune thrombocytopenia. The MS fills by circumferential flow before blood passes outward to the MZ. Many capillaries supply the MS and MZ, their arrangement and degree of branching differing among species. Capillaries never terminate within the reticulum of the white pulp. In immune thrombocytopenia, marked vascular hyperplasia occurs within white pulp and MZ. The perimarginal cavernous sinus plexus (PMCS), found in human, dog and rat, comprises large flattened spaces up to 300 microns x 1000 microns in area and 30-100 microns thick. It lies between the MZ and red pulp or directly adjacent to white pulp, and receives flow principally via the MZ. In sinusal spleens, the MS, MZ and PMCS are drained by open-ended venous sinuses. In non-sinusal spleens, the MS and MZ are drained by pulp venules. Approximately 90% of the splenic inflow passes through the region bordering the white pulp, bypassing the filtration beds of the red pulp. This suggests that immunologic functions of the spleen take precedence over the filtration of blood cellular elements in the red pulp.