Summary: Microglia are the resident macrophage-like cells of the central nervous system. Like other immune cells, microglia migrate in response to a wide variety of molecules that are produced during disease processes. This migration leads to significant accumulation of microglia at lesion sites. Once there they can perform either beneficial or harmful actions, based on the specific stimuli present in a given disease state. Thus, modulating microglial migration is an intriguing possibility for treatment of CNS diseases, where ideal strategies would be to increase the accumulation of beneficial microglia or decrease the accumulation of harmful ones. My research has focused on two stimulators of migration, adenosine-5'-triphoshate (ATP) and Complement 5a (C5a), and one inhibitor, lysophosphatidic acid (LPA). Using a technique that I developed to measure cell migration by near-infrared fluorescence, I found that ATP and C5a stimulate migration through unique signal transduction pathways. I also found that LPA inhibits both the basal migration of microglia and their migration toward ATP and C5a. Taken together, these results suggest a mechanism for fine-tuning migratory responses of microglia which may be useful for the treatment of CNS diseases.