In seven normal subjects and five asthmatics we have compared the effects of inhaled histamine with that of betahistine (a relatively selective H1-receptor agonist) and that of impromidine (a relatively H2-receptor agonist) on pulmonary epithelial permeability, as measured by the half-time clearance from lung to blood of inhaled 99mTc-DTPA (t1/2LB). Both histamine and betahistine produced statistically significant falls in baseline t1/2LB and peak expiratory flow rate, while impromidine produced no significant effects on either parameter. Similar results were obtained in normal subjects and asthmatics alike. In four of the normal subjects, histamine-induced falls in t1/2LB and peak expiratory flow rate were prevented by oral pretreatment with terfenadine 120 mg but not by cimetidine 400 mg. Histamine-induced increases in lung permeability and bronchoconstriction are both mediated via H1-receptors in normal and asthmatic subjects.