Chronic idiopathic urticaria (CIU) might be refractory to standard therapies. For the patients with severe unremitting CIU who have failed to benefit from conventional therapy with antihistamines, other effective and safe therapeutic modalities are required. A randomized, single-blind, placebo-controlled crossover study was conducted to evaluate the efficacy and safety of the new selective leukotriene antagonist montelukast sodium in the treatment of refractory CIU. Thirty patients with refractory CIU were enrolled in the trial. After informed consent was obtained, patients were randomly assigned to 2 groups. The patients in group A received 10 mg/d montelukast and a nonsedating H(1) antihistamine (cetirizine) when needed for 6 weeks. After a 2-week washout period, they received placebo for 6 weeks and the same H(1) antihistamine as needed. Group B received the treatment vice versa. Improvement was monitored by using the self-estimated urticaria activity score, which is the sum of the wheal number score and the itch severity score, and the antihistamine counts used in each study period. More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy (P <.001). H(1) antihistamine use was also significantly less frequent during the montelukast period (P <.001). There were no significant side effects with montelukast therapy. The present study results suggest that montelukast might be an effective and safe therapeutic agent in the treatment of refractory CIU.