BACKGROUND Antihistamines are first-line therapy for the treatment of seasonal allergic rhinitis (AR); however, an oral decongestant is often added to improve control of nasal congestion. OBJECTIVE To examine whether a tablet combining the nonsedating antihistamine desloratadine and the decongestant pseudoephedrine was more effective than either drug administered alone in reducing the symptoms of seasonal AR, including nasal congestion. METHODS In this multicenter, double-blind study, participants (N = 598) with symptomatic seasonal AR were administered either a combination tablet of desloratadine 2.5 mg/pseudoephedrine 120 mg (DL/PSE) bid, a desloratadine 5.0 mg qd and a placebo tablet, or pseudoephedrine 120 mg bid. Participants assessed their symptom severity twice daily over the 2-week treatment period. RESULTS The primary variable to assess the effects of the antihistamine component--mean change from baseline in average AM/PM reflective total symptom score (TSS), excluding nasal congestion--was significantly greater (-6.54) for DL/PSE than for desloratadine (-5.09) or pseudoephedrine (-5.07) monotherapy (P < .001 for both). The primary variable to assess the effects of the decongestant component--mean change from baseline in average AM/PM reflective nasal congestion score--was also significantly greater (-0.93) for DL/PSE than for desloratadine (-0.66) or pseudoephedrine (-0.75) (P < .001 vs desloratadine; P = .006 vs pseudoephedrine). CONCLUSIONS This study demonstrated that DL/PSE therapy was more effective in reducing symptoms of seasonal AR, including nasal congestion, than the individual components when administered alone, thus supporting use of this combination in participants with symptomatic seasonal AR and prominent nasal congestion.