In order to find out whether the concept of regional heterogeneity in astrocytes also applies to the immunoreactive phenotype, we studied cultured primary rat astrocytes originating from five different brain regions (cortex, hippocampus, striatum, septum, and brainstem).We investigated this heterogeneity through the ability of lipopolysaccharide (LPS) to differentially induce several parameters that are known to characterize activated astroglia: major histocompatibility complex (MHC) class II and intercellular adhesion molecule (ICAM)‐1 expression, nitric oxide (NO) production, synthesis of interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α). Under basal conditions, some of these parameters are already heterogeneic. The presence of LPS enhances these differences: expression of MHC class II increases after a 48‐hour incubation with LPS, with brainstem and hippocampus astrocytes reaching the highest levels; NO production is induced by an LPS incubation, with the brainstem showing low NO production levels; septum and striatum instead show higher cytokine (TNF‐α, IL‐6) productions. The baseline expression of ICAM‐1 also shows major regional differences, with the brainstem diplaying the highest ICAM‐1 expression. Our results demonstrate that the immunoreactive abilities of astrocytes show regional heterogeneities. This specialization may be implicated in the pathophysiological pathways of several neurodegenerative disorders. J. Neurosci. Res. 57:941–952, 1999. © 1999 Wiley‐Liss, Inc.