Our objective was to use rapid dynamic SPECT to study the effect of hygroscopic growth on aerosol deposition in the lung. Six healthy volunteers inhaled radiolabeled ((99m)Tc-DTPA) saline aerosols of two different droplet sizes (MMAD Small 3.2 +/- 0.2 and Large 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively) and tonicities (normal saline, NS, 0.9% and hypertonic saline 'HS' 7.0% NaCl) reproducibly on 4 occasions. Simultaneous emission-transmission scanning with a triple detector gamma camera was used to collect the lung images. Regional lung deposition was quantified by the penetration index or PI. The results revealed significant differences of aerosol deposition in the lung, which follows precisely the expectation from particle size and hygroscopicity. The difference in the PI values between the aerosols increases in the order of: Large NS-Large HS < Small NS-Small HS < Small HS-Large NS < Small HS-Large HS < Small NS-Large NS < Small NS-Large HS.