BACKGROUND Recent reports have attempted to redefine the accepted diagnostic criteria for allergic fungal rhinosinusitis (AFRS), a form of chronic rhinosinusitis (CRS) with nasal polyps. As a result, the existence of AFRS as a distinct entity has been questioned, suggesting that allergy has no role in CRS with sinonasal eosinophilia, and the condition should be referred to as eosinophilic fungal rhinosinusitis. The purpose of the study was to differentiate between AFRS and CRS by studying antibody responses in these two clearly defined patient groups. METHODS Ninety-nine patients were enrolled and classified as AFRS or CRS (without AFRS). Serum total IgE, IgG anti-Alternaria-specific antibodies (UniCAP 100), and IgE antifungal antibodies (immunoblotting) were compared between the groups. RESULTS Sixty-four patients fit the traditional criteria for AFRS, with 35 as CRS. Mean serum total IgE and mean IgG anti-Alternaria-specific antibodies were statistically significantly increased in AFRS over CRS patients. There was also a statistically significant increase in the mean number of IgE antifungal bands from AFRS compared with CRS patients. CONCLUSIONS We have shown a clear immunologic difference between AFRS and CRS patients. The overwhelming evidence of increased total IgE and fungal-specific IgE in AFRS supports an allergic component in AFRS. IgG anti-Alternaria-specific antibodies also point to an exaggerated fungal immune response in these patients. These results support the existence of AFRS as a separate, distinct entity of CRS. It is important to recognize AFRS to ensure proper treatment in these patients.