The purpose of this study was to replicate findings from an earlier pilot study in which we found a dose-related effect of the opioid antagonist naloxone on tic behavior in patients with Tourette's syndrome (TS). Fifteen subjects with TS were challenged with randomized doses (30 and 300 microg/kg) of naloxone at 3-day intervals. Videotaped recordings of tic behavior were counted in a "blind" fashion. We found that naloxone had opposite effects on tics at different dosages. The low dose caused a significant decrease in tics, whereas the high dose caused a significant increase in tics. Therefore, activity at opioid receptors appears to influence the expression of TS, and the difference in response to naloxone in TS subjects may be based on a dose-response effect.