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Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, and toxic chemicals that are present in air, water, soil, sediment, and biota (including fish). Most previous studies of PBDEs in fish were spatially focused on targeted waterbodies. National estimates were developed for PBDEs in fish from lakes and reservoirs of the conterminous US (excluding the Laurentian Great Lakes) using an unequal probability design. Predator (fillet) and bottom-dweller (whole-body) composites were collected during 2003 from 166 lakes selected randomly from the target population of 147,343 lakes. Both composite types comprised nationally representative samples that were extrapolated to the sampled population of 76,559 and 46,190 lakes for predators and bottom dwellers, respectively. Fish were analyzed for 34 individual PBDE congeners and six co-eluting congener pairs representing a total of 46 PBDEs. All samples contained detectable levels of PBDEs, and BDE-47 predominated. The maximum aggregated sums of congeners ranged from 38.3 ng/g (predators) to 125 ng/g (bottom dwellers). Maximum concentrations in fish from this national probabilistic study exceeded those reported from recent targeted studies of US inland lakes, but were lower than those from Great Lakes studies. The probabilistic design allowed the development of cumulative distribution functions to quantify PBDE concentrations versus the cumulative number of US lakes from the sampled population.