Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs) and pyrazolone derivatives resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions or inhibition of the cyclooxygenase pathway of arachidonic acid metabolism, stimulating the production of leukotrienes (LTs) and decreasing the production of prostaglandins (PGs), has not been presented. In this study, two types of specific IgE antibodies have been found in six serum samples from eight ASA-sensitive patients with salicyloyl and O-methylsalicyloyl disks using the Radio Allergo Sorbent Test (RAST), whereas no positive result could be found with acetylsalicyloyl disks. Further investigation on the specificity of these IgE antibodies and the chemical structure of their epitopes were performed by cross-inhibition studies. The results are in favor of an IgE-dependent mechanism involved in ASA sensitivity, and suggest that determination of specific IgE antibodies would be a safe diagnostic method for ASA sensitivity in vitro.