In some patients with asthma, aspirin (ASA) and all nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase enzymes (cyclooxygenase-1 and -2) precipitate asthmatic attacks and naso-ocular reactions. This distinct clinical syndrome, called aspirin-induced asthma (AIA), is characterized by a typical sequence of symptoms, intense eosinophilic inflammation of nasal and bronchial tissues, combined with overproduction of cysteinyl-leukotrienes (Cys-LTs). At baseline, cys-LT urinary excretion is augmented, and ASA administration leads to its further temporary increase. After ASA challenge, cys-LTs are released into nasal and bronchial secretions and can be collected in the urine. LTC4 synthase, the terminal enzyme for cys-LT production, is markedly overexpressed in eosinophils and mast cells from bronchial biopsy specimens of most patients with AIA. An allelic variant of LTC4 synthase that enhances enzyme transcription is associated with AIA. Avoiding ASA and nonsteroidal anti-inflammatory drugs does not prevent progression of the inflammatory disease. Corticosteroids continue to be the mainstay of therapy, and anti-LT drugs are also indicated for treatment of the underlying disease. After ASA desensitization, daily ingestion of high doses of ASA reduces inflammatory mucosal disease symptoms, particularly in the nasal passages, in most patients with AIA.