PROJECT SUMMARY/ABSTRACT A former Naval Air Warfare Center in Warminster Township, Bucks County, PA, and the Horsham Air Guard Station in Horsham Township, Montgomery County, PA, have been found to be the source of widespread drinking water contamination from per- and polyfluoroalkyl substances (PFAS) that went undetected for decades. Drinking water contamination was attributed to use of PFAS-containing aqueous film-forming foam (AFFF), a fire suppressant used in military training exercises. The PA site is characterized by high magnitude, long duration, and wide-ranging exposure. RTI International, the PA Department of Health (DOH), Brown University, and Temple University propose to jointly conduct research at the PA site as part of ATSDR's multisite study. The proposed site is densely populated (>80,000) and has verified perfluorooctane sulfonate and perfluorooctanoic acid contamination in public water systems (PWS) and private wells. Eligible adults and children ages 4–17 will have been exposed in the last 15 years. Adults occupationally exposed to PFAS in chemical manufacture, as a firefighter, or during fire training exercises using AFFF, will be excluded from the study. Likewise, children whose birth mothers were occupationally exposed will not be eligible. A two-stage clustered sampling design will be employed, with households selected in the first stage, followed by the sampling of all adults and children in households. Consistent with findings from a pilot biomonitoring effort conducted by PA DOH, residences served by PWS closest to the two military bases had higher serum PFAS levels and will be oversampled. A total of 2,000 adults and 800 children will be recruited for participation in the study and will complete ATSDR's core protocol, including consenting and interviewing, anthropometric measurements, neurobehavioral assessments, and biospecimen (blood and urine) collection. In addition to collecting core data on 2,800 participants, historical water reconstruction of PFAS concentrations in drinking water around the site will be conducted. Pharmacokinetic modeling will be conducted to estimate historical serum concentrations of nonoccupational-exposed people. Two investigator- initiated research activities are also proposed. First, advanced spatial analysis methods will be applied to model PFAS exposure and other potential cancer determinants over time in relation to a range of cancer endpoints. Second, exposure estimates will be leveraged to conduct a focused investigation of kidney and thyroid cancers using a family-based design. The inclusion of the PA site and the investigator-initiated research proposed in this application will contribute significantly to the scope and rigor of ATSDR's multisite PFAS environmental health study.