Microglia are the immune cells of the brain and after neural injury they are the first to respond. Depending on input from the environment, microglia either support neuronal survival or phagocytize damaged neuronal tissue. The factors involved in the communication between damaged neurons and microglia are largely unknown. Microglia migrate towards a chemotactic signal emerging from the site of neural injury. Chemokines might be involved in this signalling because they are potent inducers of cellular migration. We have recently shown that the chemokine CCL21 is upregulated in neurons after cellular injury in vitro and in vivo. Furthermore, CCL21 potently attracts microglia as shown by migration assays via the chemokine receptor CXCR3. In CXCR3 knockout animals microglial activation after injury was almost absent. Also neuronal survival was much higher when compared to the wild type animals. Microglial CXCR3 is also activated by CXCL10, another chemokine that is expressed in neurons. We have investigated and compared the expression and distribution pattern of CXCL10 with that of CCL21 in vitro. CXCL10 appears to be expressed constitutively whereas CCL21 is inducible. Both chemokines are packed in vesicles but their localization is different. For example, CXCL10 is present in the nucleus whereas nuclear CCL21 positivity is not. These results show for the first time that two chemokines that act on the same receptor in microglia are differentially regulated by neurons.