BACKGROUND Aspirin idiosyncrasy can present with bronchospasm or cutaneous reactions, but combined pulmonary and cutaneous reactions are rare. High-dose acetaminophen has been reported to provoke bronchospasm in aspirin-sensitive asthmatic patients. METHODS We report an asthmatic adolescent female who had anaphylaxis with 650 mg acetaminophen after tolerating 325-mg doses for years. She subsequently in sequence had urticaria with aspirin and ibuprofen, and anaphylaxis with sodium salicylate. She was then challenged with acetaminophen, 325 mg orally. RESULTS Approximately 30 minutes after acetaminophen challenge, she developed rhinoconjunctivitis, urticaria, pruritus, cough, and bronchospasm reversed with antihistamines and bronchodilators. CONCLUSIONS Aspirin sensitivity has not frequently been described in younger age groups. This patient also had several unusual features in that she presented first with sensitivity to acetaminophen that was then followed by aspirin sensitivity. She had urticaria with both aspirin and sodium salicylate; she had combined pulmonary and cutaneous reactions to both acetaminophen and aspirin, which are rarely described; and she had anaphylaxis with low-dose acetaminophen.