The National Centers for Disease Control and Prevention (CDC) provides an ongoing assessment of the US population's exposure to environmental chemicals by using biomonitoring in conjunction with CDC's National Health and Nutrition Examination Survey (NHANES). Characterizing the distributions of concentrations of environmental compounds or their metabolites in the US population is a primary objective of CDC's biomonitoring program. Historically, this characterization has been based on individual measurements of these compounds in body fluid or tissue from representative samples of the population. Pooling samples before making analytical measurements can reduce the costs of biomonitoring by reducing the number of analyses. For the first time in NHANES 2005–2006, a weighted pooled‐sample design was implemented to facilitate pooling samples before making analytical measurements. This paper describes this design and the estimation method being developed in the National Center for Environmental Health, Division of Laboratory Sciences (NCEH/DLS) to characterize concentrations of polychlorinated and polybrominated compounds. We present percentile estimates for 2,2  ′ ,4,4  ′ ,5,5  ′ ‐hexachlorobiphenyl (PCB153) in specific subpopulations of the US based on the NHANES 2005–2006 pooled‐sample design. We also compare estimates based on individual samples from NHANES 2003–2004 with estimates based on artificially created pools from NHANES 2003–2004 using a pooled‐sample design similar to the one used for NHANES 2005–2006. For NHANES 2005–2006 the number of analyses required to characterize the levels of 61 polychlorinated and 13 polybrominated compounds in the US population was reduced from 2201 to 228. At a cost of $1400 per analytical measurement, this represents a savings of approximately $2.78 million. Published 2012. This article is a US Government work and is in the public domain in the USA.