Concern over perfluorinated organic compounds (PFCs), e.g., perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), is due to a number of recent studies which show that the PFCs are persistent, bioaccumulative, and toxic in animals. Despite sustained interest in this topic, little information is available concerning the environmental distributions of the compounds. In this study, a new method was developed for the analysis of 10 target PFCs and its performance was examined in a systematic evaluation of surface water in the Cape Fear River Basin in North Carolina. One hundred samples from 80 different locations were collected during the spring of 2006. Detectable levels of the target PFCs were found in all samples, and were comparable to values reported previously, with maximum PFOS at 132 ng/L, PFOA at 287 ng/L, perfluorononanoic acid (C9) at 194 ng/L, and perfluoroheptanoic acid (C7) at 329 ng/L. In general, the lowest concentrations of the PFCs were found in the smallest tributaries while the highest levels were found in middle reaches of the Drainage Basin. Variability of PFC concentrations suggests a series of source inputs throughout the Basin. Seventeen sample sites (22%) had PFOS concentrations greater than 43 ng/L, a conservative safe water concentration estimated to be protective of avian life. In addition, a total of 26 sites (32%) had PFOA concentrations above 40 ng/L.