The concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (HMPG) in the cerebrospinal fluid (CSF) of patients with clinical frontotemporal dementia (FTD; n = 30), early onset Alzheimer's disease (EAD; n = 33), late onset Alzheimer's disease (LAD, n = 27) and normal controls (n = 31) were determined using HPLC. ANCOVA showed no significant effect of neuroleptic medication, extrapyramidal signs, myoclonia or gender on the CSF levels of the monoamine metabolites. Homovanillic acid was significantly reduced in all diagnostic groups (FTD, p = 0.0002; EAD, p = 0.016; LAD, p = 0.013). 5-Hydroxyindoleacetic acid was significantly reduced in EAD (p = 0.013) and in LAD (p = 0.0014), and HMPG was reduced in LAD only (p = 0.020). HMPG was significantly higher in FTD compared to EAD (p = 0.0005) and LAD (p = 0.0003). CSF-5-HIAA was significantly reduced in patients with antidepressant medication (p = 0.006). ANCOVA within the FTD group showed no significant effect of neuroleptic or antidepressant medication, extrapyramidal signs, myoclonia, gender or FTD subtype on the CSF levels of the monoamine metabolites. The results suggest that CSF-HMPG might differentiate FTD from EAD and LAD, but not from normals.