BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, and the need to identify a safe alternative drug is a common problem in clinical practice. We assessed the tolerability of the selective cyclooxygenase-2 inhibitor celecoxib in a group of NSAID-sensitive patients. PATIENTS AND METHODS: 77 patients (24 males, 53 females, age 31-80 years) with a history of adverse reactions to NSAIDs underwent standardized skin prick, scratch and patch tests along with oral, placebo-controlled blinded exposure to celecoxib (maximum single dose 200 mg, cumulative daily dose 350 mg). RESULTS: 21 patients had a history of cutaneous reactions only (urticaria), 25 had encountered respiratory symptoms (asthma), 18 reported cutaneous as well as respiratory symptoms, and in 13 patients an anaphylactoid shock occurred. Acetylsalicylic acid triggered symptoms in 38 patients. In 46 cases, several NSAIDs of different chemical groups caused symptoms. Oral challenge with celecoxib was tolerated by all 77 patients without adverse effects. CONCLUSION: This study demonstrates that celecoxib does not have cross-intolerance to NSAIDs. Celecoxib is a safe alternative in subjects with previous adverse reactions to NSAIDs.