Background: Levocetirizine and desloratadine are mostly used as H1-antihistamines in the treatment of allergic disease in 5 and 10 mg doses. Objective: In this study, the efficacy of single oral dosages of 5 and 10 mg desloratadine and levocetirizine were compared by using histamine-induced wheal and flare reactions. Methods: Eighty healthy volunteers were randomized for four double-blinded treatment with desloratadine 5 and 10 mg and levocetirizine 5 and 10 mg. Wheal and flare responses were produced by histamine. Measurements were performed just before the ingestion of antihistamines (baseline) and afterward at 30, 60, 240 min and 24 h. The values obtained for each antihistamine were compared with baseline values. Results: It was found that except the flare reactions at 30th min, levocetirizine 5 and 10 mg suppressed histamine-induced wheal and flare reactions more than desloratadine 5 and 10 mg did. There were not any significant differences between desloratadine 5 and 10 mg in all periods. Levocetirizine 10 mg suppressed wheal and flare reactions significantly more than levocetirizine 5 mg only at 24th h. Conclusion: In this study, it was observed that levocetirizine 5 and 10 mg had a higher activity than desloratadine 5 and 10 mg.