Twenty-seven patients with aspirin (ASA) sensitivity were studied. 14 patients had naso-ocular-bronchial reactions after taking ASA while others had cutaneous and gastrointestinal reactions. The oral challenges with salicylic acid (SA), O-methylsalicylic acid (OMSA), ASA, and the determination of IgE antibodies specific to salicyloyl, O-methylsalicyloyl, acetylsalicyloyl using correspondent disks by RAST, RAST inhibition and RAST cross inhibition assays were performed. The findings suggest that OMSA seems to be the main offender responsible for cutaneous and gastrointestinal reactions, whereas ASA is responsible for naso-ocular-bronchial reactions. The clinical cross reactions between ASA and ASA-like drugs (nonsteroidal anti-inflammatory drugs and pyrazolone drugs) are probably due to ''inborn errors of metabolism'. The results indicate that genetic factors, mast-cell heterogeneity, and the interindividual variability in drug metabolism, combined with immunological background should be considered as underlying mechanisms.