Knowledge about the regional deposition of aerosol particles is essential in order to perform efficient inhalation therapy or to minimize health risks due to environmental or occupational aerosol particles. In this study, 2 techniques were used to measure thoracic deposition and to differentiate between bronchial and alveolar deposition. The first technique was the clearance-derived regional deposition (CRD) technique and the second the single-breath regional deposition (SBRD) technique. Deposition was measured in 12 patients with alpha1-antitrypsin deficiency and symptoms of moderate to severe chronic obstructive pulmonary disease (COPD) using monodisperse test particles with aerodynamic diameters of 2, 3, and 4 microm. In CRD, the kinetic of particle clearance within the first 24 hours after inhalation was used to determine bronchial and alveolar deposition. In SBRD, the longitudinal distribution of deposited inert test particles was used to calculate the particle fraction deposited within and distal to the dead space. Both techniques delivered very similar mean values for total and alveolar deposition. Due to controlled slow and deep inhalations, alveolar deposition was as much as 50%. Therefore, SBRD can be considered as an easy tool to study alveolar deposition in patients.