Aerosol mixing resulting from turbulent flows is thought to be an important mechanism of deposition in the upper respiratory tract (URT). Since turbulence levels are a function of gas density, the use of a low density carrier gas would be expected to reduce deposition in the URT. We measured aerosol deposition in the respiratory tract of 8 healthy subjects using both air and heliox, a low density gas mixture containing 80% helium and 20% oxygen, as the carrier gas. The subjects breathed 0.5, 1, and 2 microm-diameter monodisperse polystyrene latex particles from a reservoir at a constant flow rate (approximately 450 mL/sec) and tidal volume (approximately 900 mL). Aerosol concentration and flow rate were measured at the mouth using a photometer and a pneumotachograph, respectively. Deposition was 17.0%, 20.3%, and 38.9% in air and 16.8%, 18.5%, and 36.9% in heliox for 0.5; 1, and 2 microm-diameter particles, respectively. There was a small but statistically significant decrease in deposition when using heliox compared to air for 1 and 2 microm-diameter particles (p < 0.05). While it could not be directly measured from these data, it is likely that when breathing heliox instead of air, deposition is reduced in the URT and increased in the small airways and alveoli.