In order to investigate the contribution of histamine to bronchoconstriction provoked by inhaled allergen and adenosine monophosphate (AMP), we have observed the effects of prior treatment with the potent H1-receptor antagonists, terfenadine and astemizole. Nine mild, atopic asthmatics underwent inhalation challenge tests on 6 separate days with histamine, allergen extract, and AMP using single concentrations previously shown to produce a 30% fall in FEV1. For each agonist, bronchoprovocation was performed 3 h after treatment with either terfenadine 180 mg or matched placebo, and airway caliber assessed by measurement of FEV1 over a period of 45 min. AMP challenge was also performed after prior treatment with astemizole. After placebo, histamine produced rapid bronchoconstriction, reaching a maximum within 5 min and returning to within 10% of baseline at 25 min. Pretreatment with terfenadine abolished the bronchoconstrictor response to histamine completely. In contrast, bronchoconstriction provoked by allergen after placebo was slower in onset and sustained during the 45 min of observation. Terfenadine only partially inhibited this response to allergen by 50 +/- 10% (mean +/- SEM) with the maximal effect being observed within the first 5 to 8 min of challenge. AMP inhalation provoked rapid bronchoconstriction similar in time course to that of histamine, and this reaction was inhibited by 86 +/- 8.1% by terfenadine. Astemizole produced inhibition of the response to AMP that was almost identical to that of terfenadine. On the basis of in vitro studies, we interpret these differential effects of terfenadine as reflecting the contribution of histamine to the various airway challenges.(ABSTRACT TRUNCATED AT 250 WORDS)