Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine beta family of chemoattractants that has been shown to play a major role in the initiation of monocyte and T cell inflammation to sites of tissue injury. In this study, we have examined the distribution of MCP-1 expression in inflammation in the central nervous system (CNS) associated with the autoimmune disease experimental autoimmune encephalomyelitis (EAE) and compared the results with those detected in inflammation associated with trauma. In EAE, MCP-1 expression was detected at the onset of inflammation, prior to clinical expression of disease, in lymphocytes and endothelial cells in subarachnoid locations. Monocyte infiltration into these areas appeared 24 h later. After the onset of clinical signs, MCP-1 expression was widely distributed in the spinal cord with levels increasing and decreasing in association with disease activity. Lymphocytes, macrophages, astrocytes, and endothelial cells could be identified as sources of MCP-1 by immunoreactivity and in situ hybridization. A similar close correlation between macrophage infiltration and the levels of mRNA for MCP-1 was found in the CNS of rats subjected to trauma, and in these animals MCP-1 was detected by immunohistochemistry in macrophages and endothelial cells. The results support the conclusion that MCP-1 is an important mediator of inflammation in the CNS.