Background Rhinoconjunctivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during the pollen season. It has recently been demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during the inflammatory response which follows allergic reactions. Objective The aim of the present study (placebo-controlled, double-blind, randomized) was the evaluation of the antiallergic activity of Terfenadine in the model of the allergic rhinitis due to natural pollen exposure. Methods Two groups of patients with pollen allergy were enrolled in this study. Ten patients were treated with Terfenadine (120mg/die) for 7 days and 10 with placebo. Evaluation criteria were: (a) clinical: signs and symptoms (recorded daily in a diary card by patients); (b) cytological: inflammatory cell count (neutrophils, eosinophils, metachromatic cells) from nasal lavage at TO and T7; (c) immunocytochemical: ICAM-1/CD54 expression on nasal epithelial cells at TO and T7; and (d) mediators dosage (ECP-MPO) on nasal lavage at TO and T7. Results As opposed to the placebo group, patients treated with Terfenadine showed a significant improvement of both symptoms (P < 0.022) and signs P < 0.001), a significant reduction of inflammatory cells infiltrate (P < 0.005), of ECP levels (P < 0.002) and ICAM-1 expression on nasal epithelial cells (P < 0.005). Conclusions In conclusion, these data demonstrate that Terfenadine exerts antiallergic activity since it is able to reduce inflammatory cell infiltrate and downregulates ICAM-1 expression.