Recent electrophysiological studies in patients with cranial dystonia (CD) have demonstrated evidence for hyperactivity of brainstem interneurons. Tizanidine (Tz), a centrally acting skeletal muscle relaxant, is thought to act by antagonizing the activity of excitatory interneurons which mediate hypertonic processes (e.g. spasticity). Theoretically this agent may be effective in patients with CD. Ten patients were enrolled in an open-label study with a single-blind placebo wash-in. Eight patients tolerated doses of between 28-36 mg per day. For the most part tizanidine was ineffective for the symptoms of CD. This failure suggests that the reported brainstem interneuronal disturbances may not be altered by Tz. Further studies using concomitant electrophysiological assessment would be necessary to assess this possibility. Alternatively, these disturbances may not be a principle cause of the dystonic movements. The finding of similar changes in other basal ganglia diseases lacking CD (e.g. Parkinson's disease) favours this latter explanation.