The goal of this study was to determine whether selegiline (L-deprenyl), a selective monoamine oxidase B inhibitor and antioxidant, would improve neuroleptic-induced tardive dyskinesia (TD). Thirty-three patients with TD were randomly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1, 2, 4, and 6 for TD, parkinsonism, akathisia, depression, and positive and negative symptoms. Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination. Twenty-eight subjects completed at least 1 week of treatment; all five dropouts were receiving selegiline. When baseline score and gender were controlled, the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group. The two treatment groups did not differ in any other outcome measure. Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial. This may be the result of the dopamine agonist effects associated with selegiline.