• The cause of multiple sclerosis (MS) is not known. This article presents a review of recent studies concerned with the development of oligodendrocytes and suggests that the primary lesion in MS could be related to damage to oligodendroglial progenitor cells. Loss of the capacity to generate oligodendrocytes could alter the course of normal development such that insufficient cells are produced to support growth and replace cells lost through attrition, and as a result, regions of demyelination appear. The site and extent of the primary loss of oligodendroglial precursors would then predetermine the time of onset, site, and severity of the neurologic manifestations of MS. It is suggested that MS is a single, continuous process and that clinical, pathologic, and immunologic findings may be understood as the consequences of the acquired inability to generate sufficient oligodendrocytes to maintain myelin.