1. Airway responses to inhaled salbutamol were measured in two groups of six normal non-atopic subjects. In each group there was a dose-dependent increase in specific airways conductance after salbutamol inhaled in cumulative doses from 25 to 600 μg.
2. In the first group these studies were repeated weekly during and after the subjects had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 500 μg four times daily by week 4. Then, while subjects were continuing to receive regular salbutamol, the studies were repeated after 48 h of inhaled sodium cromoglycate (20 mg four times daily) and again after 48 h of beclomethasone dipropionate (200 μg four times daily).
3. In the second group the studies were repeated after 10 days of regular inhaled salbutamol (500 μg four times daily).
4. There was no change in airway response to inhaled salbutamol after 4 weeks or 10 days regular salbutamol therapy, or after 48 h of sodium cromoglycate or beclomethasone dipropionate therapy.
5. This study did not show the development of resistance to β-agonists in the airways of normal subjects. These findings are discussed in the context of other studies which have shown the development of resistance, and we suggest that there may be a spectrum of susceptibility to the development of impaired airway responsiveness following regular treatment with β-adrenergic drugs.