We studied the clinical efficacy of mexiletine, a derivative oral form of lidocaine, for treatment of spasmodic torticollis. One of the nine subjects of this study was previously reported. Before starting oral mexiletine, normal saline was first injected intravenously as placebo control; lidocaine infusion then followed and clinical evaluation was provided by dystonia rating scale scores, videotape recordings, and surface electromyographic recording. In all patients, lidocaine injection resulted in a decrease of dystonic muscle contractions within 5 minutes and the effect lasted approximately 1 hour. With gradual increase of mexiletine dose, similar clinical improvement was obtained with oral doses ranging from 450–1200 mg/day for more than 6 months. Side effects in six of nine patients included upper gastrointestinal symptoms, dizziness, ataxia, and dysarthria. These were tolerable or medically manageable; only one patient required a small reduction in mexiletine dose. Strong positive correlation was found between serum and cerebrospinal fluid (CSF) mexiletine concentrations with a CSF/serum ratio of 0.6 (r = 0.96, p = 0.0005) suggesting its effective penetrance into the central nervous system. We suggest that oral mexiletine therapy may be a safe and effective treatment for spasmodic torticollis.