Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age-related increase in CSF protein and AChE activity and a significant correlation (p less than 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean +/- SD = 17.5 +/- 3.6 and 15.3 +/- 4.4 nmol/min/ml, respectively) were significantly lower (p less than 0.05) than in 13 age-matched control subjects (21.5 +/- 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p less than 0.05) in subjects with an early onset compared to those with a late onset (16.4 +/- 3.4 and 19.7 +/- 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18-month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.