alpha 2-Macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2M-R/LRP) is a multi-functional cell-surface receptor that has been implicated in diverse physiologic processes. In normal human brain, alpha 2M-R/LRP is expressed principally by pyramidal neurons with localization to cell bodies and proximal processes. By contrast, alpha 2M-R/LRP is not present in either the cell bodies or processes of most normal macroglia (including astrocytes). In this investigation, we studied the expression of alpha 2M-R/LRP in the brain, following tissue injury or neoplastic transformation, by immunohistochemistry. Significantly increased alpha 2M-R/LRP immunoreactivity was identified in reactive astrocytes, indicating the expression of this receptor is regulated in vivo in response to brain injury. alpha 2M-R/LRP immunoreactivity was also detected in glial cell tumors; this finding is novel since malignant transformation is typically thought to turn off expression of this receptor.