Background: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). Objective: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. Methods: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. Results: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P < .02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P less than or equal to .003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P < .02), less nasal secretions (P < .001), and less severe symptoms, including nasal congestion (P < .002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. Conclusion: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.