This study assesses the possible impact of changes in the morphometry of acinar airways and air spaces on the efficacy of intrapulmonary gas mixing for sulphur hexafluoride (SF 6 ) relative to that for helium (He). To that end the alveolar ventilations of He and SF 6 were determined in patients with macroscopic lung emphysema and in healthy subjects. He-SF 6 washout tests were performed in 17 patients (15 emphysema, 2 chronic bronchitis) and 21 healthy subjects. Using a three-compartment model, the data obtained were used to estimate the overall, effective, alveolar ventilations of SF 6 and He, and their ratio VaA S F 6 /Va H e . Mean VaA S F 6 /Va H e (+/-S.D.) for patients (0.80+/-0.06) was significantly smaller (P<0.001) than the value for the group of age-matched healthy subjects (0.90+/-0.05) which was non-significantly smaller than the result for the group of young, healthy subjects (0.93+/-0.03). In our patients, we also determined a score for emphysema using high resolution computed tomography, and this score correlated inversely with VaA S F 6 /Va H e (r=-0.56, P=0.018). We have interpreted our observations to mean that in patients with lung emphysema, the efficacy of intrapulmonary gas mixing for SF 6 as compared with that for He reflected by VaA S F 6 /Va H e is diminished due to increased diffusive path-lengths within the enlarged air spaces of their lungs which impair diffusive gas mixing for SF 6 more than for He.