Although a number of papers have given useful information on splenic microcirculation by light and/or scanning electron microscopy, controversies remain as to the vascular arrangement, especially in the human spleen. The present study re-examined the microvasculature of the human spleen using a three-dimensional reconstruction of immunohistochemically stained tissue sections, and showed that the central artery does not directly issue follicular arteries in the human spleen; follicular arteries are derived from penicillar arteries outside the follicle and end in the white pulp. We found that the splenic follicle is surrounded by an elaborate system of anastomosed capillaries in both the marginal zone and the superficial layer of the white pulp. Most of these capillaries are also branches of the penicillar arterioles that are issued from the central artery in the same, or a different, white pulp system. Because the endothelia of these capillaries are widely open in the marginal zone, this vascular network may play a major role in supplying blood to the marginal zone. The accumulation of sialoadhesin-positive macrophages was also observed around the vascular network, suggesting an important role for this structure as the front line of immune response.