Planar gamma camera scintigraphy is a well-established technique for characterising the deposition and clearance of radiolabelled aerosols. While single-photon emission tomography (SPET) can offer superior assessment of radioaerosol deposition and better differentiation between peripheral and central deposition, the long acquisition times of single-headed SPET have largely prevented its use for measuring clearance or deposition of fast-clearing radioaerosols. This study investigated the feasibility of fast dynamic SPET imaging (1 min/frame) using a three-headed gamma camera to assess the regional and total deposition and clearance of different radioaerosols over a period of 26 min. Six subjects inhaled nebulised technetium-99m diethylene triamine penta-acetic acid radiolabelled aerosols with small and large droplet sizes [mass median aerodynamic diameter (MMAD) 3.2 +/- 0.2 and 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively] and in normal (0.9%) or hypertonic (7%) saline with controlled breathing on four separate occasions. The penetration indices (PIs) calculated from the SPET data for normal saline were 0.50 +/- 0.04 and 0.36 +/- 0.02 for the small and large droplet sizes, respectively. Consistent with the hygroscopic growth of the hypertonic aerosols, the PIs for hypertonic saline were lower, at 0.43 +/- 0.02 and 0.34 +/- 0.02 for the small and large droplet sizes, respectively. PIs calculated from the planar data showed similar trends, but failed to detect the significant difference seen with SPET between small normal and small hypertonic saline radioaerosols. In conclusion, the feasibility of using fast dynamic SPET for imaging radioaerosol deposition and associated radiolabel clearance in the lung has been successfully demonstrated. The fast SPET was able to reveal important differences in aerosol deposition that were not detected by planar imaging.