Staphylococcus aureus-derived enterotoxins (SEs) have been implicated in the pathogenesis of airway inflammatory diseases, especially nasal polyposis. However, the exact role of these molecules in the regulation of eicosanoid synthesis in this pathology remains unexplored. We studied the possible impact of SE-induced immune responses on the eicosanoid production in nasal polyp (NP) patients. Tissue sample homogenates from NP patients, with (NP-SEs[+]) and without detectable IgE-antibodies to SEs (NP-SEs[-]; ImmunoCap system), were assayed for IL-5, myeloperoxidase, leukotriene CJD4/E4 (LTC4/D4/E4), LTB4, lipoxin A4, total IgE, and eosinophil cationic protein. Inflammatory makers, eicosanoids, and total IgE were significantly increased in NP-SEs(+) compared with NP-SEs(-) tissues, with the exception of myeloperoxidase, which was similar in both groups. Eicosanoid concentrations correlated to IL-5 and eosinophil cationic protein; however, only cys-leukotriene levels correlated with IgE-antibodies to SEs, independently of allergy and asthma. Eicosanoid synthesis is up-regulated in polyp tissue of patients with immune response to SEs and seems to be related to the inflammatory reaction induced by these enterotoxins.