The biological potency of the three LT modifiers used in this study differed, with montelukast displaying the greatest potency in our mixed cell system proliferation assay. These findings were somewhat anticipated, particularly when considering the previously reported differences in bioaffinity and activity among these compounds.27–29 Indeed, montelukast has a 20-fold higher relative affinity for the cysLT1 receptor than BAY u9773,27 and the latter has not only cysLT2 receptor antagonistic properties but also partial agonist properties, particularly at higher concentrations.27 The rationale for exploring the potential advantages of zileuton was based on its inhibitor properties of the 5-lipoxygenase pathway, which results in the formation of LTs, including LTB4 and the cysLT, and thus activates all four known LT receptors: BLT1, BLT2, cysLT 1, and cysLT 2. A 2007 reformulation30 of this compound into an effective controlled-release oral agent in the management of asthma further enhances its potential for use in the treatment of pediatric OSA. However, our findings would suggest a relatively lower potency and efficacy for zileuton in the context of pediatric sleep-disordered breathing, particularly when considering not only the higher concentrations required for reducing proliferative rates in adenoids and tonsils but also its lower antiinflammatory effect, as evidenced by the less prominent reductions in proinflammatory cytokines in the supernatants. These findings were somewhat anticipated based on the following considerations: the concentrations of LTs (both B4 and cysLT) were previously found to be increased in tonsillar tissues of children with OSA.17 Therefore, even without addition of LTD4, blocking of the cysLT receptor with montelukast should theoretically reduce the proliferative stimulus conferred by LTs, and in fact these predictions were confirmed by the experimental data. As far as the zileuton effect, this compound would, as already mentioned, block 5-lipoxygenase, and therefore would reduce or block altogether the intrinsic production of LTs, therefore leading to an antiproliferative effect. However, when such effect of zileuton was bypassed by addition of the downstream product (ie, LTD4), then zileuton should not be and indeed was not effective in reducing cellular proliferation. Notwithstanding, although the mechanisms underlying the different responses have yet to be precisely delineated, and the usefulness of any of the three agents remains to be established in the clinical setting, current findings would support the use of montelukast as the first choice in the anti-LT armamentarium.