After inhalation, C15O2 (T1/2 = 2 minutes) rapidly diffuses into pulmonary blood and is cleared from the lungs within 10 seconds. The purpose of this study was to determine whether impaired clearance of inhaled C15O2 from oligemic zones, distal to areas of obstructed pulmonary blood flow, could be detected by serial pulmonary imaging with a positron camera. Experimental obstruction of branches of the pulmonary artery was induced in 19 anesthetized dogs by inflation of balloon-tipped catheters (8-12 mm in diameter), injection of radiopaque silicone spheres (0.5-4.0 mm), and embolization with barium-impregnated autologous blood clots (1-5 mm) via the right external jugular vein. After a single bolus injection of 2 mCi of C15O2 into the endotracheal tube, serial lung images of 15O activity were obtained over 60-180 seconds. Obstruction of pulmonary arterial branches resulted in visualization of discrete zones of impaired 15O clearance which varied in area with catheter diameter. Location and size of these zones were confirmed by repeat imaging after direct injection of 15O-labeled blood through the distal catheter lumen. In dogs receiving autologous clots (n = 8), similar zones of impaired 15O clearance were consistently imaged, and single emboli as small as 2 mm in diameter produced regions of retained 15O activity. Zones of retained 15O activity corresponded to the location of radiopaque emboli on chest radiographs. This study introduces a new technique of radionuclide imaging for detection of pulmonary emboli that is noninvasive, safe, sensitive, and repeatable at short intervals.