S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cells depending on its concentration. Since serum S100B levels has been tested as a potential marker in neuropsychiatric disorders, and structural abnormalities on glial cells have been recently associated with bipolar disorder patients, we conducted this preliminary study to examine if S100B serum levels are altered during first manic episode. We quantitated S100B in serum of 40 subjects (20 unmedicated patients during manic episode and 20 healthy matched controls). The mean+/-S.D. values for S100B for bipolar subjects were 0.065+/-0.068 microg/l and 0.018+/-0.029 microg/l for healthy controls. Increased levels of S100B in bipolar mania was statistically significant (Wilcoxon signed ranks test, Z=-2.45, P=0.01). These preliminary findings suggest that mania may increase the levels of S100B in serum of bipolar disorder patients, which could be related to adaptative neural mechanisms in bipolar mania.