Tourette syndrome (TS) is a childhood-onset and relapsing disorder characterized by involuntary simple or complex tics and high co-morbidity with behavioral anomalies. Its pathophysiologic mechanisms remain unclarified. We investigated immunologic alternations and serum heavy metal levels in patients with TS to elucidate the unclarified mechanisms. Based on the Yale Global Tic Severity Scale, fifteen TS subjects (four females) aged 8-34 (mean: 15.4 +/- 6.7) in exacerbation with mean severity score 40.3 +/- 14.6 were enrolled in this study. The immunoglobulin levels were normal except for higher immunoglobulin E levels (in 10 patients) with atopy. In exacerbation, there were reverse CD4/CD8 (in two), higher percentages of natural killer cells (in five) and memory T cells (in eight), diminished lymphocyte activation CD69 marker (in three) and impaired NK cytotoxicity (in six) that showed a trend of lower inhibitory CD94 (NKG2A), activating NKp46, and perforin expression compared to those of patients with stable TS and healthy controls, but similar granzyme expression. Serum ASLO, mycoplasma antibody and the levels of heavy metals were not significantly different. All aforementioned immune alterations returned to the normal ranges except for the consistently higher memory T cells. Our study demonstrated that, in some patients with TS, consistently higher memory T cells and lower cytotoxicity in exacerbation status reflect immune alterations and underscore the potential for immunomodulation or immunosuppressive treatment.