We developed a new assay for plasma or serum G4 acetylcholinesterase (AChE) activity. There was no difference in G4 AChE activity between serum and plasma. Plasma AChE activity in control subjects (8-92 years) was independent of age. Serum G4 AChE activity was significantly increased in patients with vascular dementia (P less than 0.01), compared with age-matched control, and significantly decreased in those with probable Alzheimer-type dementia (P less than 0.02). The difference between VD and ATD was significant (P less than 0.001), and thus the measurement of plasma or serum G4 AChE activity would be helpful in the differential diagnosis of dementia.