In most patients with aspirin and nonsteroidal antiinflammatory drug (NSAID) intolerance, antiinflammatory treatment is a clinical problem. In this study we evaluated the tolerance to a new nonsteroidal antiinflammatory drug, nimesulide (Aulin, Boehringer Mannheim, Italia), in 429 patients presenting with clear histories of intolerance to NSAIDs. Nimesulide has been chosen due to its weak inhibitory action on cyclooxygenase and its peculiar mechanism of action. We carried out a single-blind challenge with cumulative doses of nimesulide administered on three different days, until the therapeutic dose of 200 mg or intolerance symptoms were reached. Nimesulide has been well tolerated in 418 subjects and only 11 patients (3.3%) showed a positive test. Our study demonstrates that nimesulide seems to be a suitable drug in aspirin hypersensitivity.