Between 1961 and 1971 US military forces dispersed over 19 million gallons of phenoxy and other herbicidal agents in the Republic of Vietnam, including over 12 million gallons of dioxin-contaminated Agent Orange, yet only comparatively limited epidemiological and environmental research has been carried out on the distribution and health effects of this contamination. As part of a response to a National Academy of Sciences’ request for development of exposure methodologies for carrying out epidemiological research, a conceptual framework for estimating exposure opportunity to herbicides and a geographic information system (GIS) have been developed. The GIS is based upon a relational database system that integrates extensive data resources on dispersal of herbicides (e.g., HERBS files records of Ranch Hand aircraft flight paths, gallonage, and chemical agent), locations of military units and bases, dynamic movement of combat troops in Vietnam, and locations of civilian population centers. The GIS can provide a variety of proximity counts for exposure to 9,141 herbicide application missions. In addition, the GIS can be used to generate a quantitative exposure opportunity score which accounts for quantity of herbicide sprayed, distance, and environmental decay of a toxic factor such as dioxin and is flexible enough to permit substitution of other mathematical exposure models by the user. The GIS thus provides a basis for estimation of herbicide exposure for use in large-scale epidemiological studies. To facilitate wide-spread utilization of the GIS, a user-friendly software package, the Vietnam Herbicide Exposure Assessment System©, was developed to permit researchers to assign exposure opportunity scores to troops, locations, or individuals.