Montelukast is a competitive antagonist of the cys LT1 receptor with an affinity that is similar, but lower than that of leukotriene D4. (5) We and others have previously reported good clinical response to montelukast in patients with eosinophilic gastroenteritis. (6-9) Recently, Vanderhoof and Young (8) reported eight patients with dysphagia, diarrhea, and/or constipation associated with tissue eosinophilia who had prolonged remission of symptoms with montelukast therapy. This experience prompted us to undertake a double-blinded placebo-controlled cross-over trial of montelukast in dyspeptic children with duodenal eosinophilia. We were able to demonstrate the superiority of montelukast as compared to placebo in the relief of pain. (9) Despite an average duration of pain of nearly 22 months prior to study enrollment, approximately one-half of the patients became pain free or nearly pain-free during the two week course of therapy with montelukast. Also of interest from this particular study was the finding that montelukast pharmacokinetics, and thus exposure, were different than previously observed in children receiving the drug. Specifically, the average population elimination t-1/2 for montelukast in our subjects (1.8 hours) was substantially shorter than mean values for this parameter (3.4 hours) determined from children without concurrent intestinal disease. (5, 10) While the reasons for this apparent disparity are not clear, it is possible that local montelukast metabolism (ie., in the small intestine) may vary as a consequence of disease state. Nonetheless, what remains to be determined is whether there is a link between systemic and tissue levels and whether an exposure-response relation can be established for montelukast in pediatric patients with eosinophilic duodenitis.