To examine the role of the cholinergic system in Tourette syndrome, we administered intramuscular physostigmine and scopolamine hydrobromide to 10 patients, evaluating both motor tics and involuntary vocalizations. Patients showed a consistent abatement of motor tics and exacerbation of vocal tics after scopolamine injection. The scopolamine effect was reversed by physostigmine. These data suggest that the cholinergic system plays a role in the pharmacologic patho-physiology of Tourette syndrome. The pharmacology of vocal and motor tics may differ, and cholinergic manipulation may benefit some patients.