The fate and transport of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) released into the environment of South Vietnam (SVN) as a consequence of the aerial application of the herbicidal defoliant Agent Orange (AO) were simulated for a generic upland forest scenario and followed over a 50-year period (1965, 1968 and 1970 onwards). Modeled concentrations of TCDD in the environment were then used as inputs to a human exposure model, which focused on long-term exposures via the food chain. Intake rates and body burdens of TCDD were estimated for adult males over the course of the simulation period and compared to available biomonitoring data. One of the most important factors determining the magnitude of the simulated human exposure to TCDD was the fraction of the chemical deposited directly to soil (where it was assumed to have a degradation half-life of 10 or 15years) relative to the fraction assumed to remain on/in the forest canopy following the spray application (where it was assumed to have a degradation half-life of ≤48h). The simulated body burdens under the various scenarios considered were broadly consistent with the biomonitoring data from SVN collected in the mid-1980s to late 1990s. Taken together, the modeling results and empirical data suggest that highly elevated exposures to TCDD (i.e., body burdens in the several 100s of pg/g lipid range and greater) were not common among people inhabiting upland forest locations in SVN sprayed with AO and that peak and average body burdens were broadly similar to those of the general population of the U.S. in the 1970s and early 1980s. The model-based assessment is consistent with the 'hot spot' hypothesis i.e., potential exposures to TCDD linked to activities conducted on or near former bases where AO was stored are greater than potential exposures in areas subjected to aerial spraying.