Histopathology of multiple sclerosis is defined by a chronic inflammatory process and the presence of large confluent plaques of demyelination. Ongoing disease activity is due to an active inflammatory process, mainly mediated by T lymphocytes and macrophages, and is associated with blood-brain-barrier damage. B lymphocytes and plasma cells are present especially in the lesions that occur during the late chronic stage of the disease. Although all plaques are characterized by demyelination, the patterns of oligodendroglia destruction and of damage to other tissue elements, such as axons and astrocytes, are variable in different cases. Oligodendrocytes are less affected by plaques that develop during the first bouts of the disease than by those plaques arising after several years of disease duration. Our data indicate that mechanisms of plaque formation may vary in different multiple sclerosis patients and in different stages of the disease process.