We studied 21 COPD patients in stable clinical conditions to evaluate whether changes in lung function induced by cumulative doses of salbutamol alter diffusing capacity for carbon monoxide (DL(CO)), and whether this relates to the extent of emphysema as assessed by high resolution computed tomography (HRCT) quantitative analysis. Spirometry and DL(CO) were measured before and after cumulative doses of inhaled salbutamol (from 200 microg to 1000 microg). Salbutamol caused significant increments of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and flows at 30% of control FVC taken from both partial and maximal forced expiratory maneuvers. Functional residual capacity and residual volume were reduced, while total lung capacity did not change significantly. DL(CO) increased progressively with the incremental doses of salbutamol, but this became significant only at the highest dose (1000 microg) and was independent of the extent of emphysema, as assessed by radiological parameters. No significant changes were observed in CO transfer factor (DLCO/VA) and alveolar volume (VA). The results suggest that changes in lung function induced by cumulative doses of inhaled salbutamol are associated with a slight but significant increase in DL(CO) irrespective of the presence and extent of emphysema.