IgE antibodies specific for staphylococcal superantigens (SAg) have been implicated in the pathology of several allergic diseases such as rhinosinusitis, nasal polyposis, asthma, and aspirin intolerance. We sought to determine whether SAg-specific IgE levels associate with clinical parameters in patients with aspirin-intolerant asthma (AIA), as compared with patients with aspirin-tolerant asthma (ATA) and nonatopic controls. Eighty patients with AIA, 62 patients with ATA, and 52 normal controls were enrolled in this study. Total serum IgE and IgE specific for staphylococcal enterotoxin A, staphylococcal enterotoxin B, and staphylococcal toxic shock syndrome toxin 1 (TSST-1) were measured using the CAP system (Pharmacia, Uppsala, Sweden). The prevalence of staphylococcal enterotoxin B-specific IgE and TSST-1-specific IgE was significantly higher in the asthma patients than in the healthy controls. The prevalence of SEB-specific IgE was slightly higher in patients with AIA than in those with ATA (22.5% versus 14.5%), although this difference was not statistically significant. No significant difference in staphylococcal enterotoxin A-specific or TSST-1-specific IgE was found between AIA and ATA subjects. Total serum IgE levels were higher in asthma patients with detectable SAg-specific serum IgE than in those without. Airway hyperresponsiveness, as measured by PC20 methacholine, was significantly increased in asthma patients with detectable SAg-specific IgE than in asthma patients without (p = 0.038). There were no significant differences in other clinical parameters between AIA and ATA patients with and without detectable SAg-specific antibody responses. These findings suggest that the staphylococcal SAg may contribute to airway inflammation and the development of airway hyperresponsiveness in asthma.