Lunar dust presents a potential toxic challenge to future explorers of the moon. The extent of the inflammatory response to lunar dust will in part depend on where in the lung particles deposit. To determine the effect of lowered gravity, we measured deposition of 0.5 and 1 μm diameter particles in six subjects on the ground (1G) and during short periods of lunar gravity (1/6G) aboard the NASA Microgravity Research Aircraft. Total deposition was measured during continuous aerosol breathing, and regional deposition by aerosol bolus inhalations at penetration volumes (Vp) of 200, 500 and 1,200 ml. For both particle sizes (dp), deposition was gravity-dependent with the lowest deposition occurring at the lower G-level. Total deposition decreased by 25 and 32% from 1G to 1/6G for 0.5 and 1 μm diameter particles, respectively. In the bolus tests, deposition increased with increasing Vp. However, the penetration volume required to achieve a given deposition level was larger in 1/6G than in 1G. For example, for dp = 1 μm (0.5 μm), a level of 25% deposition was reached at Vp = 260 ml (370 ml) in 1G but not until Vp = 730 ml (835 ml) in 1/6G. Thus in 1G, deposition in more central airways reduces the transport of fine particles to the lung periphery. In the fractional gravity environment of a lunar outpost, while inhaled fine particle deposition may be lower than on earth, those particles that are deposited will do so in more peripheral regions of the lung.