Inhalation and the subsequent deposition, retention and clearance of particles play a pivotal role in pulmonary medicine. It has been widely accepted that inhaled insoluble particles which are deposited in the conducting airways are largely cleared within 24 hours by the mucociliary escalator. Recent reports, however, suggest that this view should be revised. We therefore investigated by light and electron microscopy the number and location of particles retained in the intrapulmonary conducting airways of hamsters as a function of time. The number of retained particles was estimated unbiasedly with a novel stereological method, the fractionator. Seven male Syrian Golden hamsters inhaled an aerosol of 6 microns polystyrene particles under controlled conditions. The lungs of 3 animals were fixed by intravascular perfusion 20 minutes after the inhalation, whereas those of the other 4 animals were fixed 24 hours later. Retained particles were found in all generations of the intrapulmonary conducting airways. They were submerged in the extracellular matrix in close contact with the epithelial cells between the cilia. The particles were coated by a thin layer of osmiophilic material which was interpreted as surfactant. In the lungs fixed immediately after the inhalation, 36% of the retained particles were ingested by macrophages. 24 hours after inhalation we still found 14% of the initially retained particles. 90% of these remaining particles were phagocytized. We conclude that: (1) Surfactant is important for the retention of particles in the intrapulmonary conducting airways of hamsters. (2) There is evidence for the existence of a resident population of very active airway macrophages which play a pivotal role in clearance of the retained particles.(ABSTRACT TRUNCATED AT 250 WORDS)