This Handbook provides descriptive background information and general guidance on how to access and use data from the National Health and Nutrition Examination Surveys (NHANES). This is an enormous human database that can be used to develop information suitable for use in risk assessments, and to support regulatory and policy needs of EPA. For more than 30 years, EPA has been one of many collaborating agencies that help plan and support funding of data collection through NHANES. Because only a limited number of Agency managers and staff are aware of the content and availability of this rich database, this Handbook was developed to familiarize staffs with NHANES and foster increased use of the data to support EPA needs. Despite the limitations and complex design of this survey, it is clear that NHANES is a unique, rich database that offers a tremendous amount of human health, nutrition, and exposure information, and will continue to do so into the future. It is hoped that by informing staff about NHANES, this Handbook will encourage efforts to "mine" the data to support Agency needs across the program offices. It is also hoped that innovative approaches (e.g., using geographic information systems; linking NHANES to available databases such as the National Death Index), will be developed to analyze the data in new ways that produce information that is useful to the mission of the Agency. Now that the National Center for Health Statistics (NCHS) has established their Research Data Center, it should be possible to conduct studies that were impossible in the past because of lack of access to sensitive data. Finally, more thought should be given to designing and conducting studies that make use of subjects' biological samples (blood, urine, saliva) stored by NCHS. These samples offer a rare opportunity to study potential biomarkers of exposure and/or effects on a national sample of the U.S. population and link the data to health, nutrition, exposure and socioeconomic data collected in the baseline surveys.