Edg-2 is a member of the G-protein-coupled seven-transmembrane receptor family recently identified in oligodendrocytes. Here we show that both in vitro and in vivo, Edg-2 transcripts are not detected during early stages of oligodendroglial development, but are expressed only in mature oligodendrocytes, shortly before the onset of myelination. Lysophosphatidic acid (LPA) has been reported to be a ligand of Edg-2 receptor in different cell types. However, in oligodendroglial cultures, LPA had no effect on survival, maturation, or cytoskeleton organization. In myelinating oligodendrocyte-neuron cocultures, LPA did not influence myelinogenesis. In addition, LPA failed to induce Ca2+ mobilization and had no effect on forskolin-induced cAMP accumulation. Phosphorylation of the ERK1/ERK2 MAP kinases was the only response elicited by LPA in oligodendrocytes. Therefore, in contrast to other cell types, in which LPA exerts pleiotropic effects, Edg-2-positive postmitotic oligodendrocytes display a restricted responsiveness to LPA.