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We evaluated the intracellular and extracellular biological role of S100B protein with respect to microglia. S100B, which belongs to the multigenic family of Ca²⁺‐binding proteins, is abundant in astrocytes where it is found diffusely in the cytoplasm and is associated with membranes and cytoskeleton constituents. S100B protein is also secreted by astrocytes and acts on these cells to stimulate nitric oxide secretion in an autocrine manner. However, little is known about the relationship between S100B and microglia. To address this issue, we used primary microglia from newborn rat cortex and the BV‐2 microglial cell line, a well‐established cell model for the study of microglial properties. S100B expression was assessed by immunofluorescence in primary microglia and by RT‐PCR, Western blotting, and immunofluorescence in BV‐2 cells. S100B was found in microglia in the form of a filamentous network as well …