DOI utilizes cell-based bioassays for HTS of contaminants in environmental samples. The cell-based bioassays at the U.S. Geological Survey's Columbia Environmental Research Center are responsive to dioxin-like chemicals, PAHs, and a variety of endocrine-active substances such as estrogenic, androgenic, glucocorticoid-like, progestogenic, and steroidogenic chemicals. HTS is a valuable tool for quickly and inexpensively identifying bioactive samples for further study in higher-tier assays. DOI utilizes these assays for mapping PAH-like activity in oil-contaminated groundwater, mapping estrogenic activity in sediments from the Upper Coosa River Basin, quantitating estrone in laboratory water samples, assessing fish feed for estrogenic activity, testing pure chemicals and chemical mixtures for bioactivity, and guiding chemical analysis of endocrine-active chemicals in an effects-directed analysis of sediments and water from the Chesapeake Bay watershed. Currently, nontargeted analysis of bioactive fractions from the Chesapeake Bay watershed sediments is underway for identification of endocrine-active chemicals. A similar approach will be used to identify oxygenated PAHs from oil-contaminated groundwater. Several of the cell bioassays are also undergoing mechanistic evaluation for expanded utility in screening additional types of contaminants. The cell bioassays at the Center are primarily luciferase transactivation cell bioassays and include cell lines from the EPA’s Endocrine Disruptor Screening Program and Tox21.