Markedly increased interleukin-6 (IL-6) mRNA levels occur in experimental cerebral ischemia, although the protein production and cellular sources of IL-6 remain unclear. We examined the cellular localization of IL-6 protein in gerbil brain following transient forebrain ischemia employing immunohistochemistry and Western blot analysis. The ischemia/recirculation groups revealed distinct IL-6 immunoreactivity predominantly in cortical and hippocampal neurons after 3 hours to 3 days recirculation. At 12 h recirculation, the IL-6 expression declined specifically in the hippocampus CA1. Microglia, but not activated astrocytes, also expressed IL-6 immunoreactivity. The sham group showed no apparent immunoreactivity. IL-6 protein may thus be expressed mainly in neurons following transient forebrain ischemia. Its transient decline in the CA1 at 12 h recirculation could reflect the specific vulnerability of this region.