INTRODUCTION: Pediatric tonsillitis is frequently caused by Staphylococcus aureus, which is the most common pathogen that causes serious pyogenic infections in humans and endangers human health. S.?aureus produces numerous potent virulence factors that play a critical role in the pathogenesis of the infection caused by this bacterium, and one of the most important toxins produced by S.?aureus is toxic shock syndrome toxin-1 (TSST-1). The aim of this study is to investigate the first time the levels of IFN-γ and interleukin IL-6 in TSST-1-stimulated PBMCs from pediatric tonsillitis patients and the correlation of these cytokine levels with TSST-1-specific IgG in serum. METHODS: TSST-1 gene of S.?aureus was cloned and expressed in a prokaryotic expression system, and purified recombinant TSST-1 protein was used for measuring TSST-1-specific antibodies in the serum of patients with pediatric tonsillitis caused by S.?aureus. Moreover, the levels of interferon (IFN)-γ and interleukin (IL)-6 in TSST-1-stimulated peripheral blood mononuclear cells (PBMCs) from pediatric tonsillitis patients were investigated. RESULTS: In patients with pediatric tonsillitis caused by S.?aureus, significantly higher levels of serum TSST-1-specific IgG (P?0.05) and IgG1 (P?0.05) were detected than in healthy children. Moreover, PBMCs from the patients exhibited higher IFN-γ (P?0.05) production in response to TSST-1 than did PBMCs from healthy children. In patients with pediatric tonsillitis caused by S.?aureus, the positive rate of TSST-1-specific IgG was 70%, and the patients who tested negative for TSST-1-specific IgG exhibited significantly higher levels of IFN-γ (P?0.05) and IL-6 (P?0.05) than did the IgG-positive patients, in accord, the levels of TSST-1-specific IgG correlated inversely with the levels of IFN-γ and IL-6 in patients PBMCs stimulated with TSST-1. CONCLUSIONS: TSST-1 induces humoral and cellular immunity in pediatric tonsillitis caused by S.?aureus, which suggests that TSST-1 may play an important role in the pathogenesis of pediatric tonsillitis.