Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.