The collapse of the World Trade Center (WTC) on September 11, 2001 resulted in the release of several airborne pollutants in and around the site. Perfluorochemicals including perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), which are used in soil- and stain-resistant coatings on upholstery, carpets, leather, floor waxes, polishes, and in fire-fighting foams were potentially released during the collapse of the WTC. In this pilot study, we analyzed 458 plasma samples of New York State (NYS) employees and National Guard personnel assigned to work in the vicinity of the WTC between September 11 and December 23, 2001, to assess exposure to perfluorochemicals released in dust and smoke. The plasma samples collected from NYS WTC responders were grouped based on estimated levels of exposure to dust and smoke, as follows: more dust exposure (MDE), less dust exposure (LDE), more smoke exposure (MSE), and less smoke exposure (LSE). Furthermore, samples were grouped, based on self-reported symptoms at the time of sampling, as symptomatic and asymptomatic. Eight perfluorochemicals were measured in 458 plasma samples. PFOS, PFOA, perfluorohexanesulfonate (PFHxS), and perfluorononanoic acid (PFNA), were consistently detected in almost all samples. PFOA and PFHxS concentrations were approximately 2-fold higher in WTC responders than the concentrations reported for the U.S. general population. No significant difference was observed in the concentrations of perfluorochemicals between symptomatic and asymptomatic groups. Concentrations of PFHxS were significantly (p < or = 0.05) higher in the MDE group than in the LDE group. Concentrations of PFNA were significantly higher in the MSE group than in the LSE group. Significantly higher concentrations of PFOA and PFHxS were found in individuals exposed to smoke than in individuals exposed to dust. A significant negative correlation existed between plasma lipid content and concentrations of certain perfluorochemicals. Our initial findings suggest that WTC responders were exposed to perfluorochemicals, especially PFOA, PFNA, and PFHxS, through inhalation of dust and smoke released during and after the collapse of the WTC. The potential health implications of these results are unknown at this time. Expansion of testing to include all archived samples will be critical to help confirm these findings. In doing so, it may be possible to identify biological markers of WTC exposure and to improve our understanding of the health impacts of these compounds.