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Melioidosis results from an infection with the soil-borne pathogen Burkholderia pseudomallei, and cases of melioidosis usually cluster after rains or a typhoon. In an endemic area of Taiwan, B. pseudomallei is primarily geographically distributed in cropped fields in the northwest of this area, whereas melioidosis cases are distributed in a densely populated district in the southeast. We hypothesized that contaminated cropped fields generated aerosols contaminated with B. pseudomallei, which were carried by a northwesterly wind to the densely populated southeastern district. We collected soil and aerosol samples from a 72 km2 area of land, including the melioidosis-clustered area and its surroundings. Aerosols that contained B. pseudomallei-specific TTSS (type III secretion system) ORF2 DNA were well distributed in the endemic area but were rare in the surrounding areas during the rainy season. The concentration of this specific DNA in aerosols was positively correlated with the incidence of melioidosis and the appearance of a northwesterly wind. Moreover, the isolation rate in the superficial layers of the contaminated cropped field in the northwest was correlated with PCR positivity for aerosols collected from the southeast over a 2-year period. According to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analyses, PFGE Type Ia (ST58) was the predominant pattern linking the molecular association among soil, aerosol and human isolates. Thus, the airborne transmission of melioidosis moves from the contaminated soil to aerosols and/or to humans in this endemic area. Author Summary: Cases of melioidosis, an emerging disease, are usually clustered after rains or typhoons. In Taiwan, the endemic area includes rural cropped fields contaminated with B. pseudomallei in the northwest and a densely populated district in the southeast, where melioidosis-cluster is distributed. We hypothesized that contaminated cropped fields generated aerosols contaminated with B. pseudomallei, which were carried by a northwesterly wind and enveloped the southeastern densely populated district. In a prospective study, aerosols that contained B. pseudomallei-specific DNA were well distributed in the densely populated districts but were rarely found in their surrounding areas. The concentration of specific DNA in aerosols correlated with the melioidosis incidence and the northwesterly wind in this endemic area. The isolation rate in the superficial layers of the contaminated cropped field in the northwest correlated with the PCR positivity of aerosols collected from the southeastern district over a 2-year period. We used genetic typing to identify a molecular association among the soil, aerosols and human isolates. We suggest that melioidosis is airborne and is transmitted from the contaminated soils to aerosols and/or to humans in this area. [ABSTRACT FROM AUTHOR]