Oligodendrocytes are the myelin forming glial cells of the CNS and are known to express receptors linked to ion channels and intracellular second messenger cascades. In this paper, we describe the intracellular calcium responses of cells from the oligodendrocyte lineage to application of lysophosphatidic acid (LPA), a naturally occurring, growth factor-like phospholipid. Oligodendrocyte precursors did not respond to application of LPA (1 microM). In mature oligodendrocytes, however, LPA (1 microM) induced an increase in the intracellular calcium concentration ([Ca2+]i). In the majority of cells this increase was followed by a persistent plateau phase. The LPA-induced [Ca2+]i signal vanished in Ca2+-free medium, implying that it arose due to a Ca2+ influx across the plasma membrane. Preincubation of the cells with Pertussis-toxin prevented the generation of LPA-induced [Ca2+]i signals. We conclude that cultured rat oligodendrocytes express functional LPA receptors, which mediate a transmembrane Ca2+ influx via a Pertussis-toxin-sensitive G-protein.