S100B is a predominantly astrocytic protein with dose-dependent cytotoxic and neurotrophic properties encoded on chromosome 21q22.3. Concentrations of S100B were measured in the cerebrospinal fluid (CSF) of 31 patients with Alzheimer's disease (AD), 36 patients with frontotemporal lobe dementia (FTLD) and 49 patients with other non-inflammatory neurological diseases. Additional CSF S100B concentrations were correlated with normalised brain volume measurements in AD and FTLD. CSF S100B was significantly higher in AD (Mean+/-standard deviation=0.4+/-0.2 ng/ml) and FTLD (0.42+/-0.19 ng/ml) patients when compared with control subjects (0.25+/-0.08, P<0.001). In patients with AD, S100B correlated negatively with normalised brain volume (R(S)=-0.53, P<0.001). No such correlation was found for FTLD patients. This study supports the concept that S100B is of pathological relevance for degeneration of the central nervous system in AD.