Multiple sclerosis (MS) is characterized by multifocal loss of myelin, oligodendrocytes, and axons. Potential MS therapies include enhancement of remyelination by transplantation or manipulation of endogenous oligodendrocyte progenitor cells. Characteristics of endogenous oligodendrocyte progenitors in normal human brain and in MS lesions have not been studied extensively. This report describes the distribution of cells in sections from normal adult human brain and MS lesions by using antibodies directed against NG2, an integral membrane chondroitin sulfate proteoglycan expressed by oligodendrocyte progenitor cells. Stellate-shaped NG2-positive cells were detected in the white and gray matter of normal adult human brain and appeared as abundant as, but distinct from, astrocytes, oligodendrocytes, and microglia. Stellate-shaped or elongated NG2-positive cells also were detected in chronic MS lesions. A subpopulation of the elongated NG2-positive cells expressed the putative apoptotic signaling molecule p75(NTR). TUNEL-positive cells in three active, nine chronic active, and four chronic inactive lesions, however, were p75(NTR)-negative. These studies identify cells with phenotypic markers of endogenous oligodendrocyte progenitors in the mature human CNS and suggest that functional subpopulations of NG2-positive cells exist in MS lesions. Endogenous oligodendrocyte progenitor cells may represent a viable target for future therapies intended to enhance remyelination in MS patients.