We describe a major glial cell population in the central nervcus system (CNS) that can be identified by the expression of 2 cell surface molecules, the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alpha R). In vitro and in the developing brain in vivo, NG2 and PDGF alpha R are expressed on oligodendrocyte progenitor cells but are down-regulated as the progenitor cells differentiate into mature oligoder drocytes. In the mature CNS, numerous NG2+/PDGF alpha R+ cells with extensive arborization of their cell processes are found ubiquitously long after oligodendrocytes are generated. NG2+ cells in the mature CNS do not express antigens specific to mature oligodendrocytes, astrocytes, microglia, or neurons, suggesting that they are a novel population of glial cells. Recently NG2+ cells in the adult CNS have been shown to undergo proliferation and morphological changes in response to a variety of stimuli, such as demyelination and inflammation, suggesting that they are dynamic cells capable of responding to changes in the environment. Furthermore, high levels of NG2+ and PDGF alpha R are expressed on oligodendroglioma cells, raising the possibility that the NG2+/PDGF alpha R+ cells in the mature CNS contribute to glial neoplasm.