Macrophages were examined for immunoglobulin G (IgG) and albumin in actively demyelinating lesions in two patients with multiple sclerosis (MS) using the peroxidase‐antiperoxidase immunocytochemical technique. In both cases, macrophages were present that stained for cytoplasmic or surface IgG or both. In one case, in which the tissue was rapidly fixed in chilled fixative, macrophages located among myelinated nerve fibers at plaque margins, but not elsewhere in the plaque, revealed surface IgG in the form of caps restricted to one or both poles of the cell. These caps were absent in sections stained for albumin. Because capping implies the presence of a multivalent ligand close to the cell surface and because cap formation was observed only in macrophages contacting myelin sheaths, we suggest that antimyelin antibody cytophilic for macrophages may be present in the central nervous system in MS, and that immune ligand‐mediated phagocytosis may play a role in myelin breakdown in the disease. This study provides the first direct evidence that IgG participates locally in myelin breakdown in MS.