The National Exposure Registry (NER) was created as a comprehensive group of data repositories that sought, over time, to relate specific environmental exposures to dioxin, trichloroethylene (TCE), benzene, and trichloroethane (TCA) to registrants' health conditions. Some parts of the NER were well conceived, whereas others were not. The most important design deficiency of the NER was its inability to adequately assess exposure. This was the key missing element and the Achilles heel of the NER program. At least three other important issues were never satisfactorily resolved in the design of the NER. They were unverified self-reporting, appropriate control groups, and the use of biomarkers. The many health effects that were observed to be in excess when compared with national norms might be explained by methodological differences in data analysis and reliance on self-reported nonverified data. Creating and maintaining a population-based chemical exposure registry is a more difficult challenge than creating and maintaining an outcome registry, such as a cancer registry.