Background: Cholinergic urticaria does not respond well to treatment with conventional antihistamines and is difficult to study because of its highly variable clinical expression which depends on the presence of eliciting factors. Objective: We have therefore designed a double-blind, crossover, placebo-controlled trial, with a 3-week treatment period using either 20 mg/day of cetirizine or placebo. Methods and Results: Presence of eliciting factors and symptoms were scored daily on a diary card by the patient, with a scale from 0 to 3 for erythema, wheals and pruritus. Statistical analysis was done on 11 evaluable patients during the last 2 weeks of each treatment period (to allow for 1 week of washout) and only for days when eliciting factors were present. Compared to placebo, cetirizine caused a statistically significant reduction of wheals (p=0.015), erythema (p=0.033), pruritus (p=0.006) and all symptoms (p=0.013). No adverse events were observed. Conclusion: These data show a high efficacy of cetirizine at twice its normally recommended dose which may be related to the specific antiallergic effects of this newer-generation antihistamine.