The usefulness of Xe-133 and Tc-99m-MAA single photon emission computed tomography (SPECT) in identifying areas to be resected during video-assisted thoracoscopic lung reduction surgery for emphysema was examined. Twenty-nine patients with advanced emphysema were examined using Xe-133 and Tc-99m-MAA SPECT prior to and following surgery. For the Xe-133 dynamic SPECT, patients inhaled Xe-133 gas for 6 minutes. Equilibrium and subsequent washout SPECT images were acquired every 30 seconds for 6 to 7 minutes during spontaneous breathing. Ventilation was quantified by Xe-133 clearance time (T1/2) in addition to visual assessment. The patients underwent unilateral thoracoscopic volume reduction in the regions with abnormal Xe-133 retention and Tc-99m-MAA defect. All patients demonstrated marked, heterogeneous Xe-133 retention and Tc-99m-MAA defects preoperatively. The worst functioning areas were identified as nonventilated and noflow areas, or areas with air trapping and low perfusion. These changes were found even in patients with diffuse and symmetrical impairments on chest CT. After surgery, most of these "target areas" disappeared and pulmonary function tests demonstrated significant improvement. T1/2 correlated closely with the percent predicted FEV1 (%FEV) and 6-minute walk distance before and after surgery (p<0.0001). Xe-133 and Tc-99m-MAA SPECT imaging was useful in identifying "target areas" in the emphysematous lung. Directed unilateral thoracoscopic volume reduction based on these SPECT images is an effective treatment for emphysema.