Diffuse astrocytic gliomas extensively infiltrate brain tissue and contain numerous microglial cells, but it is unknown whether these two characteristic features are pathogenetically related. We therefore studied the effects of murine microglial cells on motility of GL261 mouse glioma cells using Boyden chamber assays. In the presence of microglia, glioma cell migration occurred earlier, and after 48 h it was threefold higher as compared to incubations without microglia. This effect was mediated by substances released from microglia, because similar effects were observed by microglia-conditioned medium, and it was specific to microglia, because oligodendroglia and endothelial cells only weakly stimulated glioma cell migration. Microglia activating substances (GM-CSF, LPS) led to a further increase of motility. These data support the notion that microglia accumulation in diffuse glial tumors does not merely represent a nonspecific reaction to tissue injury, but reflects participation of these cells in supporting and promoting the invasive phenotype of astrocytoma cells.