AbstractAstrocytes from different sources bind the chemokine monocyte chemoattractant factor (MCP‐1), yet functional expression in these cells of CCR2, the major receptor for this ligand, has been a matter of controversy. Here we show that cultured human fetal astrocytes express CCR2 at the mRNA and protein levels, and display chemotaxis and calcium flux in response to MCP‐1. Surface CCR2 protein expression and MCP‐1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP‐1 exposure, supporting the argument that CCR2, and not another receptor, mediates MCP‐1 ligation in these cells. Downmodulation was further determined to occur via receptor internalization, and to apparently proceed via both clathrin‐coated vesicles and caveolae, the latter being a novel mode for the endocytosis of chemokine receptors. Insofar as MCP‐1 is thought to mediate inflammatory and developmental processes within the central nervous system (CNS), such astrocyte responses to this chemokine are likely to significantly impact physiological and pathophysiological events at the blood‐brain barrier and within the CNS parenchyma. © 2002 Wiley‐Liss, Inc.