BACKGROUND: Controlled trials have demonstrated the efficacy of antihistamines in the treatment of chronic idiopathic urticaria. Second-generation antihistamines are recommended as first-line therapy for chronic idiopathic urticaria. The purpose of this study was to determine the effect of desloratadine, a newer, nonsedating, second-generation antihistamine, on symptoms of chronic idiopathic urticaria, disease severity, and quality of life (QoL). METHODS: In an open-label, observational, multicenter study, 348 subjects with chronic idiopathic urticaria were given 5 mg of desloratadine once daily for 2 weeks. Outcome measures included change from baseline at Day 14 using the Aerius Quality of Life Questionnaire (AEQLQ); change from baseline in pruritus score, number and maximum size of hives, sleep quality, and activity impairment; and subjects' response to therapy. RESULTS: Desloratadine significantly decreased subjects' overall condition and symptom scores from baseline to Day 14 (2.19 +/- [SD] 0.66 and 1.14 +/- 0.89, respectively; P < 0.0001). Desloratadine treatment significantly improved all 10 AEQLQ domain scores from baseline to Day 7 and Day 14 (P < 0.0001). Sleep disturbance scores decreased 40% from baseline to Day 7 (1.42 +/- 1.03 to 0.85 +/- 0.89, respectively), and interference with daily outdoor activity scores showed a 41% decrease from baseline to Day 7 (1.11 +/- 0.98 to 0.66 +/- 0.90) (P < 0.0001 for both). There were significant reductions in itching, size of hives, and hive score at both Days 7 and 14. Treatment resulted in moderate, marked, or complete relief of symptoms in 76.2% of subjects. Desloratadine was well tolerated, with no adverse events reported. CONCLUSION: In an open-label, observational study, desloratadine 5 mg once daily significantly decreased symptoms of chronic idiopathic urticaria and improved subject QoL.