We have investigated the effects of the intravenous administration of three anticholinergic drugs (atropine, benztropine, and chlorpheniramine) with variable antihistaminic properties in comparison with saline in adult-onset focal dystonias. In many patients, the severity of the involuntary movements varied from one observation to the next. Patients with spasmodic torticollis, writer's cramp, and segmental dystonia showed little change with any of the active drugs. The occasional individual who improved by more than 20% did so at the expense of drug-induced drowsiness. We conclude that cholinergic mechanisms are not of general importance in the pathogenesis of these conditions. However, the beneficial response to benztropine and chlorpheniramine in two of 20 patients emphasizes the continuing need for a trial-and -error approach in the therapy of these focal dystonias.