Previous studies have reported alterations of glial cells and particularly astrocytes in mood disorders. Therefore, serum concentration of the astrocytic marker S100B was ascertained with an immunoluminometric assay in 20 patients with mood disorder and 12 healthy age-matched controls. Serum S100B was elevated in major depression (median after admission 410 ng/l, at discharge o 100 ng/l) and mania (130,160 ng/l), when compared with controls (o 100 ng/l; p o 0.01). Antidepressive treatment reduced S100B in conjunction with severity of depressive symptoms (p o 0.01). The severity of depression (Hamilton Depression Rating Scale) was positively correlated with S100B (r s ¼ 0.51, p o 0.005). Elevated serum S100B during depressive and manic episodes of mood disorders may indicate alterations of astrocytes, which are reversed by antidepressive treatment. NeuroReport 13:1675^1678