We have developed a model which successfully reconstructs the lifetime polychlorinated biphenyl (PCB)-101 burden of the UK population for individuals born between 1920 and 1980. It not only follows burdens and clearance of persistent organic contaminants throughout a human lifetime — taking changes in age and body composition into account — but also, importantly, incorporates changing environmental concentrations of the compound of interest. Predicted results agree well with available measured lipid concentrations in human tissues. Its unique construction takes into account both changing environmental concentrations of PCBs in principal food groups and changing dietary habits during the time period. Because environmental burdens of persistent organic contaminants have changed over the last 60 years, residues in food will also have mirrored this change. Critically in this respect, the year in which an individual was born determines the shape and magnitude of their exposure profile for a given compound. Observed trends with age represent an historical legacy of exposure and are not simply a function of equal yearly cumulative inputs. We can demonstrate that the release profile of PCB-101 controls levels in the food supply and ultimately the burden of individuals throughout their life. This effect is expected to be similar for other PCB congeners and persistent organic compounds such as polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs). Models of this type have important applications as predictive tools to estimate the likely impact of source-reduction strategies on human tissue concentrations.