Background: Events in developing cutaneous late-phase allergic reactions can be characterized by a combination of skin chamber and biopsy approaches. In some previous studies, cetirizine reportedly inhibited mediator release and/or inflammatory cell responses in late-phase reactions. Objective: This study was carried out to determine the effects of cetirizine on early late-phase reactions by using skin chamber and skin biopsy specimens. Methods: Skin chamber responses during a 6-hour challenge with pollen antigens were assessed in 15 sensitive subjects during randomized, crossover treatment with cetirizine (20 mg/day) or placebo for 7-day periods with measurements of humoral and cellular components. Biopsy specimens of the underlying dermis sere obtained. Results: During cetirizine treatment, there was significant (p < 0.01) inhibition of immediate wheal and flare reactions to pollen antigens (34, 46%), codeine (41, 65%), and histamine (35, 68%). However, gross late-phase reactions at 6 hours mere unaffected. During both cetirizine and placebo treatment, there was significantly greater accumulation at antigen sites in: (1) skin chamber levels of histamine, total cells, lactoferrin, and eosinophil cationic protein; (2) eosinophils (total and activated) on appended cover glasses; (3) deposition of lactoferrin and eosinophil cationic protein in the underlying dermis. However, these responses were not significantly differed during cetirizine treatment compared with placebo treatment periods. Conclusion: A persistent pattern of inflammatory cell accumulation with release of granule proteins during early late-phase reactions was unaffected by cetirizine treatment.