Antimicrobial air filters using a new natural product agent, grapefruit seed extract (GSE) have been investigated for application in air purifiers or heating, ventilation, and air-conditioning (HVAC) systems. The disk diffusion method was used to evaluate the antimicrobial activity of GSE, propolis, and shiitake against four bacteria: Staphylococcus aureus, Micrococcus luteus, Psedomonas aeruginosa, and Escherichia coli. The inactivation of S. aureus was then investigated on air filters treated with two natural products, GSE and propolis (selected for comparison to GSE) using two test methods based on different deposition weights.GSE displayed the highest antimicrobial activity against S. aureus, P. aeruginosa, and E. coli of the three natural products tested by the disk diffusion method. Similar inactivation rates of 58-67% for GSE and propolis air filters were observed at a relatively low deposition weight of 94-98 μg/cm 2 using the aerosol deposition method. However, the inactivation rate was considerably superior on the GSE air filter (~98%) compared to the propolis air filter (~75%) at deposition weights of 5000-8000 μg/cm 2 using the film attachment method. The inactivation rate for both GSE and propolis air filters could be expressed as an exponential function [in the form of 1 -exp(-ax b )] of the deposition weight per unit area of the natural product. The superior inactivation performance of the GSE air filter using the film attachment method was probably due to the high wettability of GSE for bacteria cultures, with a contact angle less than 20°. Therefore, GSE air filters will be more effective and economical than propolis air filters due to their high microbial activity and relatively low price.