It is debatable whether beta 2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of beta 2-receptor stimulation contribute to the present observations.