Acetylcholinesterase (AChE) activity in dog plasma is significantly higher than in either ventricular or cisternal CSF. However, since protein levels in plasma are about 100-fold higher than in CSF, the specific activity of AChE is lower in plasma than in CSF. Acetylcholinesterase activity in plasma represents only 22% of total cholinesterase (ChE) activity, while preliminary findings indicate that in ventricular CSF it is 50-60%. Acetylcholinesterase activity in ventricular CSF is significantly lower than in cisternal CSF. Chlorpromazine (10 mg/kg, intravenous), a drug which increases acetylcholine turnover, increased AChE-specific activity in all dogs. Our results support the hypothesis of a neuronal origin of AChE activity in CSF.