Pyritinol (former chemical name pyrithioxine) is a scavenger of free radicals and central cholinomimetic agent (Benes[caron ]ova[acute ], Krejc[caron ]i[acute ], and Pavli[acute ]k, 1991). Its therapeutic efficacy in tardive dyskinesia (TD) was tested in a 12-week double-blind cross-over placebo-controlled trial. To our knowledge, pyritinol was used in the treatment of TD for the first time. Pyritinol (600 mg/day perorally) or placebo were administered for the 6 weeks after a one-week single-blind placebo period. The next 6 weeks the medication was reversed. The neuroleptic dosage was kept constant for the whole trial.Twelve of seventeen psychiatric inpatients (5 men and 7 women, 11 diagnosed as schizophrenia and 1 as schizoaffective psychosis according to DSM-III-R) completed the trial. The withdrawal of 5 patients was unrelated to the experimental therapy. Mean age ([plusmn]SD) of the patients group was 55.1 [plusmn] 13.8 years. TD was assessed from videotape by two independent raters, using the Abnormal Involuntary Movement Scale (AIMS).Pyritinol was significantly better than placebo in improving TD as measured by the total score of the AIMS (ANOVA, df = 2; F = 5.20; P = 0.01). Simpson and Angus Rating Scale for Extrapyramidal Side Effects, Brief Psychiatric Rating Scale (BPRS) and Structured Adverse Effects Rating Scale (SARS) did not detect any treatment emergent symptoms on 5% level of significance.Our results support both hypotheses on the importance of free radicals (Cadet et al., 1986) and central cholinergic hypofunction (Klawans, 1973) in TD development.