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The bronchodilation and cardiovascular effects of bronchodilators may alter alveolar ventilation and perfusion distribution, which could subsequently affect single-breath diffusing capacity of the lungs for carbon monoxide (DL,CO) measurements. The aim of this study was to investigate the effect of salbutamol on DL,CO in subjects with and without airway obstruction and reversibility.Sixty subjects were investigated with 20 in each of the three groups: normal spirometry; irreversible obstruction; and reversible obstruction. Baseline spirometry, plethysmographic lung volumes, DL,CO, pulse rate and arterial blood gases were measured. The same testing sequence was repeated after administration of a placebo inhaler and again after 400 μg salbutamol.Salbutamol did not affect the mean alveolar volume (VA) (P> 0.05), transfer coefficient for carbon monoxide (DL,CO/VA,KCO) (P> 0.05) or DL,CO (P> 0.05) in the normal and irreversible obstruction groups. In the reversible obstruction group, salbutamol caused an increase in the mean VA compared with placebo (P< 0.001). However, the meanKCO was reduced (P< 0.001). The mean change in DL,CO was not significant (P> 0.05). A considerable reduction in DL,CO was found after salbutamol in four subjects in the reversible group as a result of a minor increase in VA and substantial decrease inKCO. No statistical difference in pulse rate or arterial blood gases values was detected.Salbutamol had no effect on the mean DL,CO in any group. However, salbutamol may considerably reduce DL,CO in some individuals with reversibility secondary to its effects on VA andKCO.The effect of salbutamol on DL,CO was investigated in subjects with and without airway obstruction and reversibility. The findings suggest that salbutamol may considerably reduce DL,CO in some individuals with reversible airway disease secondary to its effects on VA andKCO.