The objective of present study is to investigate and compare the effects of different commercially utilized thermal treatments of 65 degrees C for 30 min, 80 degrees C for 15 s, 95 degrees C for 5 min and 137 degrees C for 5 s on the interactions between casein and f3-lactoglobulin (f3-LG) and the consequent digestion profile in simulating gastrointestinal (GI) environments. It was demonstrated, by the measurements of turbidity, polyacrylamide gel electrophoresis, and molecular affinity between f3-LG and casein, that high temperature (95 degrees C and 137 degrees C) or long heating time (30 min) significantly increased the turbidity of f3-LG and casein mixture, promoted the self-aggregates of f3-LG, and enhanced the complexation of f3-LG and kappa-casein, as a result of the intermolecular thiol and disulfide interchange, as well as the strong affinity between f3-LG and casein. Comparatively, the pasteurization of about 80 degrees C for 15 s decreased the turbidity of the model mixture of f3-LG and casein, and did not lead to f3-LG and kappa-casein aggregates cross-linked with disulfide. In addition, the affinity of the heated casein and f3-LG with the thermal treatment of 80 degrees C for 15 s was the lowest compared with the ones shown in the other three treatments. In the simulated gastric condition, the model mixture of f3-LG and casein heated at 80 degrees C for 15 s appeared to be digested faster compared with the one treated at 137 degrees C for 5 s. However, this phenomenon could not be observed obviously in the simulated intestinal condition. Therefore, the formation of disulfide between the reactive thiols in denatured f3-LG and kappa-casein accounts mainly for the f3-LG self-aggregates and the f3-LG-casein complexes in the commercially utilized thermal treatments. In terms of interactions between f3-LG and casein, pasteurization may be considered as an ideal thermal treatment of milk for heating processing, without significant impact on product properties.