Since 2005, restrictions have been because of fish consumption along the Rhone River because of high polychlorobiphenyl (PCB) concentrations, which have resulted inadverse economic consequences for professional fisheries in affected areas. French environmental authorities have expended considerable efforts to research sediment remediation strategies and development of sediment quality guidelines designed to protect the health of humans consuming Rhoˆne River fish. Here we: (1) develop a bioaccumulation food-web model that describes PCB concentrations in three common freshwater fish species of the Rhoˆne River, using Bayesian inference to estimate the input parameters; (2) test the predictive power of the model in terms of risk assessment for fish consumption; and (3) discuss the use of this approach to develop sediment quality guidelines that protect the health of humans consuming Rhoˆne River fish. The bioaccumulation model predictions are protective for human consumer of fish and are efficient for use in risk assessment. For example, 85% of the predicted values were within a factor of 5 of measured CB153 concentrations in fish. Using sensitivity analyses, the major role played by sediment and diet behaviors on bioaccumulation process is illustrated: the parameters involved in the respiratory process (contamination from water) have little impact on model outputs, whereas the parameters related to diet and digestion processes are the most sensitive. The bioaccumulation model was applied to derive sediment concentrations compatible with safe fish consumption. The resulting PCB sediment thresholds (expressed as the sum of seven PCB indicator congeners) that are protective for the consumption of the fish species ranged from 0.7 to 3 ng/g (dw).