To compare the deposition patterns of heliox-driven and air-driven radiolabeled bronchodilator aerosol, a prospective randomized study was undertaken at the Ben Taub Hospital in Houston, Texas. The working hypothesis was that nebulization with heliox would improve the peripheral deposition of a bronchodilator aerosol. Twelve mild-moderate known asthmatics were recruited for the study. They were asked to withhold medications for 8-24 hours prior to reporting for the study. Each subject was randomized to receive either heliox or oxygen for delivery of albuterol labeled with Tc-99m DTPA. Prior to the nebulization, baseline spirometry was performed. Following nebulization, the subjects were scanned for 1,000,000 counts on the ADAC Genesis Scanner. A postbronchodilator spirometry was then performed. Subjects returned about a week later, this time to have the same process repeated with the other gas. The normalized pixel counts were obtained, and the frequency distribution histograms were constructed for each of the deposition images. Skew and kurtosis were calculated. A lower skew and kurtosis value suggests a more peripheral distribution of the bronchodilator, whereas a higher pixel count corresponds with an increased area and uniformity of deposition. There were no statistically significant differences in baseline PFTs on the 2 days of the study. The pixel count was statistically higher after the heliox-driven nebulization than the air-driven nebulization. The skew and kurtosis values were lower after the heliox-driven nebulization than after the air-driven nebulization of radiolabeled aerosol. All patients had a good bronchodilator response with either driving gas. However, the degree of improvement was more with heliox-driven nebulization than with air-driven nebulization. We conclude that aerosol delivery with heliox results in more uniform and peripheral deposition. Thus, this mode of delivery can be used when uniform, peripheral deposition is desired as with drug delivery during an exacerbation or with aerosolized gene therapy.