This exploratory study was meant to determine the effect of the dopamine (DA) agonist pergolide on Gilles de la Tourette syndrome (GTS) in children and adolescents and to ascertain correlates of pergolide response. Thirty-two outpatients, aged 7-19 years, were systemically assessed in a neuropsychiatric clinic for the presence of GTS and comorbid disorders. After a 6-week open-label, fixed-flexible dosing schedule, response to pergolide on standard GTS severity outcome measures was assessed. Overall, 75% of patients (24/32) had a > 50% drop in their tic severity rating from baseline with a mean treatment dosage of 177 +/- 61 micrograms/day. Highly significant (p = 0.0001) baseline to week 6 differences were demonstrated in all tic symptom measures. The presence of restless legs syndrome (RLS) comorbidity (59%) was highly associated with a positive response. These results suggest DA agonism as a strategy, and pergolide in particular, may be a practical form of therapy for GTS. Response predictors of patient comorbid RLS argue for its further study with regard to GTS.