Multiple sclerosis (MS) is a demyelinating disease during which an autoimmune reaction is directed against oligodendrocytes. Alterations of normal myelin structure or oligodendrocyte metabolism may be primary events that influence the susceptibility to MS, Once triggered, the immune system attacks and destroys myelin and the myelin forming cell, Evidence is presented that the oligodendrocyte responds to the attack by immune cells and their secreted products through modulation of its metabolism and gene expression. Cytokines, immunoglobulins, and complement complexes may elicit a survival response in the oligodendrocytes, involving the induction of heat shock proteins and other protective molecules, The possibility of manipulating these complex glial cell functions and controlling their pathologic interactions illuminate how myelin damage can be contained and how the injured tissue can be repaired. (C) 1996 Wiley-Liss, Inc.