S100B is a cytokine with neurotrophic and neurite-extending activity that has been implicated in the mechanism of action of anti-depressants and in the pathobiology of aging associated disorders such as Alzheimer's disease. The antidepressant fluoxetine increases hippocampal S100B content in young adult rats. In humans, brain levels of S100B mRNA and protein increase with advancing age. We assayed hippocampal S100B protein content in young (2 month) and old (24 month) mice, and in old mice treated for 2 weeks with fluoxetine. Using quantitative Western immunoblotting and an immunoassay kit we found higher S100B content in the hippocampus of old mice. Fluoxetine treatment of old mice further increased hippocampal S100B, suggesting that aging does not interfere with fluoxetine's action on hippocampal S100B.