To study the dimensions of the functional gas exchange unit, spherical polystyrene beads (diam 50-500 micrometers) were injected intravenously into 12 normal anesthetized paralyzed dogs (15-24 kg wt). We argued that beads small enough to lodge within gas exchange units would not give rise to a population of high ventilation-perfusion ratio (VA/Q) areas, whereas embolization of larger vessels supplying these units would. Each dog received only one bead size in cumulative 0.25-g doses up to a maximum of 2.25 g. Multiple inert gas elimination data were obtained after each dose to monitor the development of high VA/Q regions. Injection of 50- and 100-micrometers beads never gave rise to high VA/Q regions, whereas 150-, 250-, and 500-micrometers beads consistently induced a high VA/Q mode comprising up to 45% of the ventilation. Histological examination of lungs from five additional dogs injected with small (approximately 0.5 g) doses revealed that beads rarely formed clusters and appeared in vessels of their own diameter in over 90% of instances. By the above criterion, the functional gas exchange unit in these lungs is that volume of tissue subtended by 150- micrometers-diam arteries (vessels associated with respiratory bronchioles).