The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses ofinhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second (FEV,), specific airways conductance (sGaw), and the dose of histamine causing a 20% fall in FEV, (PD20) in six subjects with mild asthma. On each of 10 occasions measurements were made of baseline FEV,, sGaw, and PD20 after 15 minutes' rest, and followed one hour later, when the FEV, had returned to baseline, by a single nebulised dose of salbutamol (placebo, 5, 30, 200 and 1000 pg) or ipratropium (placebo, 5, 30, 200 and 1000 jig) given in random order. Measurements of FEV,, sGaw, and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium. Salbutamol and ipratropium caused a similar dose related increase in FEV, and sGaw, with a mean increase after the highest doses of0-76 and 0-69 litres for FEV1 and 1-15 and 0-96 s-kPa-1 for sGaw. Salbutamol also caused a dose related increase in PD20 to a maximum of 2-87 (95% confidence interval 2-18-3-55) doubling doses of histamine after the 1000 pg dose, but ipratropium bromide caused no significant change in PD20 (maximum increase 0-24 doubling doses, 95% confidence interval -0-73 to 1 22).Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide. This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action, suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs.Several studies have confirmed an association between increased airway reactivity and diminished airway calibre in subjects with airflow obstruction'" but the cause of the association is not clear. There are reasons to expect that an increase in airway reactivity would lead to increased airflow obstruction, and vice versa that an increase in airflow obstruction would increase airway reactivity, by a combination of mechanisms.9' Alternatively, both airflow obstruction and increased airway reactivity may occur as a result of a common underlying disease process.Bronchodilator drugs such as ,B agonists, antimuscarinic agents, and methylxanthines have been shown to cause a decrease in airway reactivity in conjunction