Macrophages are prominent participants in inflammatory demyelinating neuropathies. To provide a different means of evaluating macrophage behavior, we used immunostaining of teased nerve fibers and endoneurial blood vessels. We assessed the frequency with which macrophages were seen in inflammatory demyelinating neuropathies, their relationship to normal and demyelinating fibers, and their expression of major histocompatibility Class II markers (Ia antigen). In 6 patients with chronic inflammatory neuropathy and 1 with Guillain-Barré syndrome, we found regularly that macrophages were adherent to teased blood vessels. Cells presumed to be entering the nerve were elongated, often with a polarized appearance suggesting motility, and were Ia-positive. After entry into nerve, the Ia-positive macrophages were adherent to both normal and demyelinating fibers. They often retained their Ia positivity after penetrating into the nerve fiber and removing myelin. Foamy macrophages, judged to be postphagocytic, were Ia-negative. The foamy macrophages found adhering to blood vessels were presumed to be leaving the nerve. This pattern of entry as Ia-positive prephagocytic cells and evolution to Ia-negative foamy macrophages was compared with other experimental and human neuropathies.