Nasal biopsies to naturally occurring allergic rhinitis demonstrate ultrastructural evidence of mast cell degranulation. Consistent with this, H1 antihistamines are clinically efficacious in this disorder. The nasal symptoms of itch, sneeze and discharge are, however, more susceptible to this mode of therapy than is nasal blockage. As nasal blockage is vascular, the combination of an H1 antihistamine and a decongestant has a logical rationale. To investigate the efficacy of such a combination, the influence of pretreatment with terfenadine, 60 mg, pseudo-ephedrine, 120 mg, Seldane-d (a registered trademark of Marion Merrell Dow)--a combination of pseudo-ephedrine, 120 mg, and terfenadine, 60 mg,--and matched placebo was objectively investigated on the nasal response to allergen in grass-pollen-sensitive seasonal rhinitic subjects (7 males, 7 females, age 19-56 years) in a double-blind, placebo-controlled, 4-period cross-over study. Seldane-D was significantly better than placebo in all efficacy measurements: nasal itch (p < 0.02), sneezing (p < 0.01), discharge (p < 0.01) and blockage (p < 0.003). The terfenadine component of Seldane-D contributed predominantly to the reduction in itch, sneeze and discharge (p < 0.01) while the pseudo-ephedrine component primarily contributed to the nasal airway effects (p < 0.04). These results indicate that the combination of terfenadine and pseudo-ephedrine as a single oral medication is complementary.