Randomized double-blind trials using doxepin and several conventional antihistamines were carried out for treatment of patients with idiopathic cold urticaria. In the first double-blind trial, eight of nine patients preferred doxepin (10 mg three times daily) to cinnarizine (10 mg three times daily). In the second double-blind trial, the results of ice cube tests suppressing the effect of cyproheptadine (4 mg three times daily), doxepin (10 mg three times daily), and hydroxyzine (10 mg three times daily) did not statistically differ. However, doxepin was subjectively the most effective and it had fewer side effects than other treatments that were compared. Doxepin effectively suppressed the wheal and itching responses and shortened the duration of the wheal response in the ice cube test in all patients with cold urticaria who were studied.