AIM: To evaluate the relationship between diagnosis and clinical course of Tourette syndrome and group A Streptococcus (GAS). METHOD: GAS infections, anti-streptococcal, and anti-basal ganglia antibodies (ABGA) were compared between 168 patients (136 males, 32 females) with Tourette syndrome; (median [range] age [25th-75th centile] 10y [8-11y]); median Tourette syndrome duration (25th-75th centile), 3y (1y 3mo-5y 9mo) and a comparison group of 177 patients (117 males, 60 females) with epileptic or sleep disorders median age [25th-75th centile], 10y [8y-1y 6mo]). One hundred and forty-four patients with Tourette syndrome were followed up at 3-month intervals; exacerbations of tics, obsessive-compulsive symptoms, and other psychiatric comorbidities were defined by a bootstrap procedure. The effect of new GAS infections and identification of new ABGA upon risk of exacerbation was assessed using logistic regression analysis. RESULTS: Cross-sectionally, patients with Tourette syndrome exhibited a higher frequency of GAS infection (8% vs 2%; p=0.009), higher anti-streptolysin O (ASO) titres (246 [108-432] vs 125 [53-269]; p0.05). INTERPRETATION: Patients with Tourette syndrome might be more prone to GAS infections and develop stronger antibody responses to GAS, probably as a result of underlying immune dysregulation. New GAS infections are unlikely to exert, years after their onset, a major effect upon the severity of neuropsychiatric symptoms.