A model of the absorption and desorption of persistent lipophilic organic pollutants in the human gastrointestinal tract was formulated. The influence of the dietary intake of chemical, the chemical concentration in human tissue, the physical-chemical properties of the chemical, and the sorption properties of the feces on the predicted net mass transfer of chemical was explored and shown to be consistent with experimental observations. The model was parametrized and tested using a data set of approximately 800 measurements of net absorption/excretion of polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans that were obtained in experiments with 14 human volunteers. Overall good agreement was obtained between the predicted and measured values. The largest discrepancies were observed in cases of net excretion because the model was not able to account for the considerable individual and temporal variability in the sorption properties of the feces. In a sample model application, good agreement was found between concentrations of octachlorodibenzo-p-dioxin in blood measured in different age groups of the background population and values predicted by the model.