Rationale: Little is known about clearance of ultrafine carbon particles from the different regions of the human lung. These particles may accumulate and present a health hazard because of their high surface area. Objectives: 99mTc radiolabeled 100nm diameter carbon particles were inhaled by healthy non-smokers, symptomatic smokers and by patients with chronic obstructive pulmonary disease (COPD). Methods: Using a bolus inhalation technique particle deposition was targeted either to the airways or to the lung periphery, and retention, clearance and translocation were measured using retained radiotracer imaging. Measurements and Main Results: In vitro studies determined that mean leaching of soluble 99mTc-radiotracer from the carbon particles was 4.1% (2.6% standard deviation) after 24 hours. Cumulative 99mTc-activity in urine at 24 hours was 1.1% (1.3%) of activity deposited in the lungs. In the lung periphery particle retention was not affected by smoking or pulmonary disease; retention was 96% (3%) after 24 hours . The small amount of clearance could be attributed to leaching of the 99mTc-label, suggesting negligible particle clearance. In non-smokers retention of particles targeted to the airways was 89% (6%) and 75% (10)% after 1.5h and 24h, respectively. Radiolabel activity did not accumulate in the liver. Conclusions: Within the limits of detection of our experimental system, most inhaled ultrafine carbon particles are retained in the lung periphery and in the conducting airways without substantial systemic translocation or accumulation in the liver at 48 hours. Repeated exposure may result in significant pulmonary accumulation of ultrafine particles.