The role of amyloid metabolism in the pathophysiology of frontotemporal lobar degeneration (FTLD) has yet to be elucidated. We compared CSF levels of amyloid beta 1-40 (A beta 40) and amyloid beta 1-42 (A beta 42) in patients with FTLD (n = 21) versus patients with Alzheimer's disease ( AD, n = 39) and in control subjects ( n = 30). While in AD cases Ab42 levels were lower and CSF Ab40 levels equal to those in controls, a significant decrease in Ab40 and increase in the CSF A beta 42/Ab40 ratio was observed in FTLD compared with AD and control subjects. These findings favour a differential involvement of amyloid beta peptides in FTLD compared with AD.