The effect of premedication with terfenadine, an H1 antagonist, on nasal challenge with antigen, histamine and methacholine was evaluated. A single dose of terfenadine had no effect on the response to a localized challenge with methacholine but completely blocked the secretory response to histamine on both the ipsilateral and contralateral sides. These results suggest that terfenadine has no anticholinergic activity and that the direct and reflex secretory response to challenge with histamine is mediated by the H1 receptor. A single dose of terfenadine significantly reduced sneezing and nasal secretion after challenge with antigen but had no effect on nasal congestion. A double-blind placebo-controlled clinical trial was undertaken to compare the effects of pretreatment with terfenadine for 1 week on the response to sequential nasal challenge with antigen and histamine. Terfenadine significantly reduced the number of sneezes and the levels of kinins, albumin and TAME esterase activity following challenge with antigen. The levels of histamine were also significantly reduced, suggesting inhibition of the degranulation of mast cells. The number of sneezes and the levels of albumin were also significantly reduced by terfenadine following challenge with histamine.