Characterization of natural and anthropogenic features that define the environmental settings of sampling sites for streams and groundwater, including drainage basins and groundwater study areas, is an essential component of water-quality and ecological investigations being conducted as part of the U.S. Geological Survey's National Water-Quality Assessment program. Quantitative characterization of environmental settings, combined with physical, chemical, and biological data collected at sampling sites, contributes to understanding the status of, and influences on, water-quality and ecological conditions. To support studies for the National Water-Quality Assessment program, a geographic information system (GIS) was used to develop a standard set of methods to consistently characterize the sites, drainage basins, and groundwater study areas across the nation. This report describes three methods used for characterization-simple overlay, area-weighted areal interpolation, and land-cover-weighted areal interpolation-and their appropriate applications to geographic analyses that have different objectives and data constraints. In addition, this document records the GIS thematic datasets that are used for the Program's national design and data analyses.