Oligodendrocyte precursor proliferation is precisely regulated spatially and temporally during development to allow optimal myelination of the central nervous system (CNS). We propose that a paracrine regulatory pathway involving the chemokine GRO1 and platelet-derived growth factor (PDGF) permit local control of precursor proliferation in the brain. GRO1, PDGF, and their receptors act synergistically to precisely regulate oligodendrocyte precursor proliferation in vitro and in vivo in the rat CNS. The nature of the paracrine regulatory loop with astrocyte and neuronal GRO1 expression in a pattern that is closely correlated with PDGFαR+ oligodendrocyte precursors suggests that the GRO1/PDGF regulatory mechanism provides local control of oligodendrocyte precursor proliferation during development.