Quinolinic acid, which is produced by macrophages and microglia, can kill neurons in vivo and in vitro. To test whether quinolinic acid is toxic to oligodendrocytes, glial cells cultured from the brains of 2-day-old rats were incubated with quinolinic acid at concentrations known to kill neurons. The cells were then fixed and immunostained with MAbO4 to mark immature and mature oligodendrocytes and anti-myelin basic protein (MBP) to mark mature oligodendrocytes. The data indicated up to 54% reductions in the numbers of O4-positive cells in cultures after incubation with quinolinic acid. Apoptosis of O4-positive cells began during the first 6 h, and some of the apoptotic cells became fragmented. Further apoptosis, and clumping of dead MBP-positive oligodendrocytes, occurred during longer incubation with quinolinic acid. Thus, quinolinic acid arising from macrophages and microglia during autoimmune disease may take part in a mechanism of oligodendrocyte injury and killing.