Background: Increasing evidence points toward a modifying role of Staphylococcus aureus and its products in the pathogenesis of nasal polyposis. Objective: The aim of this study was to investigate cytokine and mediator production after stimulation with S aureus-derived proteins enterotoxin B, protein A, and lipoteichoic acid in nasal polyp and control inferior turbinate tissue. Methods: Tissue fragments were stimulated with RPMI (negative control), enterotoxin B, protein A, and lipoteichoic acid for 30 minutes and 24 hours. Supernatants were measured by multiplex for proinflammatory cytokines (IL-1 beta, TNF-alpha) and T-cell and subset-related cytokines (IFN-gamma, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13). Histamine, TGF-beta 1, cysteinyl leukotrienes, and prostaglandin D-2 were analyzed by ELISA. Results: Thirty minutes of protein A stimulation resulted in a significant increase of histamine, leukotrienes, and prostaglandin D-2. Enterotoxin B stimulation over a period of 24 hours induced a significant increase of IL-10, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-10, and IL-13 in both groups, with this increase significantly higher in nasal polyps compared with controls. Conclusion: We here show that S aureus products have various effects on mucosal tissues: surface protein A induces mast cell degranulation, whereas enterotoxins induce the release of cytokines, with a T(H)2-skewed pattern in nasal polyps, supporting the stimulatory role of superantigens in the development of this inflammatory disease.