The deposition of aerosol in the human lung occurs mainly through a combination of inertial impaction, gravitational sedimentation, and diffusion. For 0.5-to 5-lm-diameter particles and resting breathing conditions, the primary mechanism of deposition in the intrathoracic airways is sedimentation, and therefore the fate of these particles is markedly affected by gravity. Studies of aerosol deposition in altered gravity have mostly been performed in humans during parabolic flights in both microgravity (lG) and hypergravity (*1.6G), where both total deposition during continuous aerosol mouth breathing and regional deposition using aerosol bolus inhalations were performed with 0.5-to 3-lm particles. Although total deposition increased with increasing gravity level, only peripheral deposition as measured by aerosol bolus inhalations was strongly dependent on gravity, with central deposition (lung depth < 200 mL) being similar between gravity levels. More recently, the spatial distribution of coarse particles (mass median aerodynamic diameter & 5 lm) deposited in the human lung was assessed using planar gamma scintigraphy. The absence of gravity caused a smaller portion of 5-lm particles to deposit in the lung periphery than in the central region, where deposition occurred mainly in the airways. Indeed, 5-lm-diameter particles deposit either by inertial impaction, a mechanism most efficient in the large and medium-sized airways, or by gravitational sedimentation, which is most efficient in the distal lung. On the contrary, for fine particles (*1 lm), both aerosol bolus inhalations and studies in small animals suggest that particles deposit more peripherally in lG than in 1G, beyond the reach of the mucociliary clearance system.