The aim of this study was to measure and compare the influence of tidal volume (Vt) respiratory rate (RR) and pMDI/spacer combination on aerosol deposition of 4 pMDI/spacer combinations, which are used for infants. An anatomically correct upper airway model of a 9-month-old infant was connected to a breathing simulator. Sinusoidal breathing patterns were simulated with; duty cycle T(i)/T(tot) = 0.42, Vt: 25, 50, 75, 100, 150, 200 ml (RR: 30 breaths/min); and RR: 20, 30, 42, 60, 78 breaths/min (Vt: 100 mL). pMDI/Spacers tested were: budesonide 200 microg/Nebuchamber, fluticasone 125 microg/Babyhaler and both budesonide and fluticasone with Aerochamber. Plastic spacers were detergent coated to reduce electrostatic charge. Spacer-output and lung dose were measured by a filter positioned between spacer and facemask or between model and breathing simulator. Particle size distribution of lung dose was assessed with an impactor during simulated breathing. Spacer-output was significantly positively correlated with Vt for all pMDI/spacers (all R > 0.77, p < 0.001), but not correlated with RR. Lung doses initially increased from Vt = 25 to 50 mL (Nebuchamber, Aerochamber) or to 100 mL (Babyhaler) and then decreased, with increasing Vt and RR (R: -0.98 to -0.82, p < 0.001). Lung doses of fluticasone were 1.5-6-fold higher compared with budesonide, irrespective of spacer type (p < 0.001). MMAD decreased with increasing Vt and RR. Dose to the lungs of particles <2.1 microm was independent of Vt and RR. Lung dose decreases with increasing inspiratory flow (increasing Vt or RR) by increasing impaction of coarse particles in the upper airways. Deposition of particles <2.1 microm is relatively flow independent. When electrostatic charge of spacers is reduced, lung dose is pMDI dependent and spacer independent.