Leukocyte migration to the central nervous system (CNS) is a common process with often devastating consequences that follows infection of this tissue compartment with a variety of viruses. The mechanisms underlying this process are poorly defined but, it is hypothesized that chemokines may be important regulatory signals for the cerebral recruitment and extravasation of leukocytes. Here we discuss this hypothesis in the context of different viral infections of the CNS with emphasis on lymphocytic choriomeningitis virus (LCMV). In general, the pattern of chemokine gene expression in these CNS viral infections is dynamic and complex with often overlapping expression of a number of different subclasses of chemokine genes. In the case of CNS infection with LCMV, cerebral chemokine gene expression was observed in euthymic and to a lesser extent athymic mice and preceded increases in cytokine gene expression and in euthymic mice, CNS leukocyte recruitment. These observations together with the finding that CRG-2/IP-10, a prominently expressed chemokine gene in many different CNS viral infections, was expressed by cells intrinsic to the CNS e.g. astrocytes, suggest that activation of chemokine gene expression may be a direct, early and localized host response to viral infection. These findings are consistent with the proposed involvement of chemokines as key signaling molecules for the migration of leukocytes to the CNS following virus infection.