Macrophaqes (MO) bring virus and circulating monocytes can bring enzymes into brain. Can a muscle autograft be the site of MO entry into normal brain? The autografts maintain a focal, chronic inflammation in the medulla adjacent to the graft. Circulating, dye-labeled MO, infused into arterial blood, enter the graft and take the first step of entering brain by adhering to medulla capillaries. Adhesion is known to be partly mediated by the interaction of LFA-1 receptors on MO, with I CAM-1 counter-receptors on vessel endothelium. I CAM-1, immunohistochemically detected, is highest in the medulla nearest the graft. Once in the medulla, MO activated by phorbol ester (TPA) prior to intravascular infusion, migrate in 2-24 h for a short distance parallel to the long fiber tracts. Thus, brain microvessels near the muscle autograft, rather than the graft itself, are the site at which MO enter brain. The longitudinal arrangement of MO signifies that MO have not merely crossed the capillary wall, but have migrated away from the vessels, because the capillaries run perpendicular, not parallel, to the fiber tracts. Major histocompatibility complexes (MHC) are not expressed in microglial (MG) cells of the normal medulla and pons, but are expressed by MG and endothelium of medulla near the grafts. MGI cells, derived from mixed glial cultures of rat brain, were treated like the MO and infused into brain vasculature. Results were similar to MO except that TPA-activated MGI cells migrated less extensively into brain than did non-activated MG cells.