Fexofenadine is a non-sedating selective third-generation antihistamine, which also exerts an antiinflammatory action. The aim of this study was to evaluate the influence on the expression of inflammatory skin mediators, together with the efficacy and tolerability, of fexofenadine in chronic idiopathic urticaria (CIU). Fexofenadine 180mg was administered once daily for 4 weeks after a placebo run-in phase of3 to 7 days. Efficacy paramaters were obtained from patients' assessment of urticaria symptoms. Non-Iesional skin of patients with active CIU was studied immunohistochemically before and after treatment. The expression of the following mediators was evaluated: adhesion molecules (ICAM-l, ELAM-l, VCAM-l)j mast cell proteases (chymase and tryptase) and proinflammatory cytokines (IL-l~, IL-3, IL-6 and TNF-n). Of the 20 subjects enrolled, 3 dropped out of the study. Treatment proved successful in most cases (88.2 %) (p <0.01) and a significant improvement of all symptoms was registered. Treatment was well-tolerated by all patients; adverse events, neither serious nor drug-related, occurred in any case. Immunochemistry revealed at the baseline a significant expression of ELAM-l, VCAM-l, tryptase, chymase, and TNF-« (p~0.05) in non-Iesional skin of patients compared to normal controls. After treatment with fexofenadine, there was a significant decrease in the expression of ELAM-l (p= 0.02), VCAM-l (p= 0.04) and tryptase (p=0.04), whereas no relevant change was observed for the other parameters examined. This work confirms the efficacy and tolerability of fexofenadine HCI 180mg in CIU. These preliminary data show a trend towards a decrease in the expression of tryptase and some adhesion molecules after treatment, suggesting an anti-inflammatory activity of fexofenadine.Chronic idiopathic urticaria (CIU) is defined as the occurrence of wheals on most days for more than six weeks in the absence of any known causative or triggering agents (1). As it is not possible to adopt specific measures of prevention in CIU, treatment hangs upon symptomatic tools, with HI antihistamines as the mainstay for patients with uncomplicated forms (2-3). Newgeneration antihistamines are usually preferred owing to the greater affinity for H 1 receptors and the lower incidence of sedation and anticholinergic effects compared with older molecules (4-5).Fexofenadine is a non-sedating third generation antihistamine with highly selective H 1-receptor antagonist activity, which has been approved for the treatment of seasonal allergic rhinitis and CIU. Controlled studies have proved the high therapeutic value and the excellent tolerability offexofenadine (6-11). The good safety profile of fexofenadine is also due to the absence of cardiotoxic effects and sedation, even at doses much higher than those recommended for aller- gic rhinitis and CIU. Moreover, fexofenadine undergoes minimal systemic metabolism and is well tolerated, also in patients with renal or hepatic impairment and in the elderly. It appears to be associated with no risk of signifi...