The purpose of this study was to examine the roles played by astrocytes in a case of rapidly progressive multiple sclerosis (MS). Within early-active and active lesions, hypertrophic astrocytes played an important role in lesion pathology through the phagocytosis of myelin and axonal debris and through the internalization of other glial cells, including astrocytes. In addition to this critical role, hypertrophic astrocytes, in areas that lack significant inflammation (within the adjacent normal appearing white matter and within late remyelinating lesions) were found to be active in myelin and axonal debris phagocytosis with no evidence of cellular internalization. Hypertrophic astrocytes therefore not only play an important role in the pathogenesis of MS lesions but also exert a continued deleterious effect upon tissue in the absence of significant inflammation. In addition, we found evidence for a significant population of vimentin-positive, glial fibrillary acidic protein (GFAP)-negative, bipolar, astrocyte precursors within the late remyelinating lesions. Their significance is not known but a possible role may include their participation in the successful remyelination of the lesion.