Based on the cholinergic-deficiency hypothesis of tardive dyskinesia (TD), we administered cytidine diphosphoryl choline (CDP-Choline) (a naturally occurring biochemical intermediary in the synthesis of phosphatidylcholine), 500 mg twice a day orally, to four women and one man with TD for 2 to 8 weeks in a double-blind, placebo-controlled crossover trial. Although the small sample size provides only limited power to detect a treatment effect, there was no evidence of efficacy, adverse effects, or changes in psychopathology.