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Background: Chronic idiopathic urticaria, daily hives that last >6 weeks, can be resistant to antihistamines, even when higher than conventional doses are used. Other pharmacologic agents have been associated with inconsistent benefit., Objective: We examined the relationship of clinical characteristics and the presence of autoimmune antibodies to antihistamine resistance in children. We further examined the efficacy and safety of cyclosporine in children whose urticaria was resistant to antihistamine., Methods: Patients referred to the pediatric allergy and pulmonary specialty clinic at the University of Iowa Children's Hospital and diagnosed as having chronic idiopathic urticaria were identified during the period from August 2008 to July 2013. A retrospective examination of treatment and outcome was performed., Results: Forty-six patients, 26 female patients and 20 male patients, with chronic idiopathic urticaria were identified. The ages of 16 patients who were antihistamine resistant ranged from 9 to 18 years (median, 12.5 years). Those patients who were antihistamine responsive had a median age of 6 years, significantly lower than those who were antihistamine resistant (P = .0001). There was no significant association between autoimmune antibodies and antihistamine resistance. All the patients who were antihistamine resistant were treated with cyclosporine; all experienced complete resolution of urticaria at times that ranged from 2 days to 3 months (median, 7 days). Relapses responsive to repeated cyclosporine occurred in 5 of the patients after 1 week to 15 months (median, 6 months). Adverse effects were not seen in these patients., Conclusion: Our data were consistent with efficacy and safety of cyclosporine for chronic urticaria in children when even high doses of antihistamines are ineffective., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)