Recently, leukotrienes have been implicated in the mediation of bronchoconstriction and inflammatory changes in asthma. Leukotriene levels have also been shown to be elevated in patients with asthma as well as in those with sinonasal polyposis and sinusitis. The leukotriene synthesis inhibitor zileuton and the leukotriene receptor antagonist zafirlukast have been shown to produce subjective and objective improvements in patients with mild to moderate asthma. Given these findings, we evaluated the efficacy of these two medications in controlling sinonasal polyposis and their associated symptoms. We treated 40 patients diagnosed with sinonasal polyposis and sinusitis with either zileuton or zafirlukast. No other change was made in their standard therapy. Outcome measures included subjective interviews and questionnaire responses, as well as office endoscopic examinations and chart reviews. At study's end, 36 patients were available for evaluation. Twenty-six had taken zafirlukast, five had taken zileuton, and five others had switched from zafirlukast to zileuton. Overall, 26 patients (72%) experienced subjective improvement in their symptomatology after starting their medication. Statistically significant improvement was noted with respect to headache, facial pain and pressure, ear discomfort, dentalgia, purulent nasal discharge, postnasal drip, nasal congestion and obstruction, olfaction, and fever. An objective alleviation, or at least stabilization, of sinonasal polyposis was seen in 50% of the patients. Four patients (11%) discontinued their medication because of side effects. We conclude that antileukotrienes might play a significant role in controlling polyposis and symptoms secondary to sinonasal disease, and they might be a viable alternative to long-term oral steroid therapy and repeated surgical debridement.