We have used human astrocytoma-derived cells to investigate the cellular responses of central nervous system cells to Toxoplasma gondii infection. At 24 h post inoculation, the secretion of CCL-2 (or Monocyte Chemotactic Protein-1) was augmented six-fold over the control. This secretion was down-regulated by D609, a specific inhibitor of phosphatidylcholine-dependent phospholipase C (PC-PLC), but not modulated by gamma interferon (IFN-gamma). Ribonuclease protection assay analyses showed significant down-regulation of CCL-2 mRNA production during infection by Toxoplasma gondii when cells were treated by D609. The mRNA levels of the seven other chemokines studied were not modified by D609. CCL-2 seems to contribute to the cell recruitment during human cerebral reactivation of Toxoplasma gondii. Cellular production of this CC chemokine during toxoplasmosis may be regulated by a PC-PLC-dependent pathway.