Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predictions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1=50-80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 mu m-diameter particles (tidal volume of I L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 mu m particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.798 +/- 0.205 vs. 0.527 +/- 0.122 mL/mL, p=0.01; MS: -0.271 +/- 0.129 vs. -0.145 +/- 0.076 mL/mL, p=0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to-moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease. (C) 2016 Elsevier Ltd. All rights reserved.