The cellular infiltrate found during the acute phase of multiple sclerosis (MS) consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during the inflammatory response. We examined the ability of human astrocytoma cell lines, as well as primary human and rat astrocytes, to generate a specific member of the intercrine/chemokine family of cytokines, RANTES, when exposed to TNF-α, IL-1β and IFN-γ. Astrocytoma cells as well as primary astrocytes produced RANTES upon incubation with TNF-α or IL-1β. IFN-γ alone did not induce RANTES production by astrocytes, but it potentiated the effects of either TNF-α or IL-1β. Induction of RANTES by TNF-α was mediated by the p55 receptor since a specific anti-p55 antiserum mimicked the effect of TNF-α. These results indicate that human astrocytes are capable of generating a cell-specific chemokine that can account for the inflammatory cellular infiltrate observed during the acute phase of MS, in a process that is regulated by cytokines.