Milk proteins are important for their nutritional value and for their functional properties. Heat treatment is commonly used in dairy technology and in some cases milk is submitted to cumulative heat treatments. However, behavior of protein during heating depends on the physico-chemical conditions and also on the presence of other molecules (sugar, protein and lipid). We hypothesized that in addition of the well- known β-lactoglobulin (β-Lg) / κ-casein (κ-CN) complexes, other kind of aggregates occur in heated milk. To gain information of the occurrence of such species, the aim of this work was to study the effects of a strong heat treatment (90 ºC with different holding times) using following model systems: purified β-Lg and β-casein (β-CN), in presence of a reducing sugar (glucose) at neutral pH heated up to 24 h; and β-Lg with other milk proteins: αS2-casein (αS2-CN) and κ-CN at neutral pH. Furthermore, we studied the consequences on the in vitro simulated digestion of the produced aggregates. To characterize aggregates formed during heat-treatment and their breakdown, we use a series of techniques: gel electrophoresis (LDS-PAGE), thioflavin T essay, transmission electron microscopy, size exclusion chromatography, fluorescence, dynamic light scattering and hydrolysis kinetics. Our results revealed that high temperatures have favored the formation of covalent bonds, others than disulphide. β-Lg fibrils were produced at neutral pH and glucose decreased aggregate formation. On the other hand, glucose accelerate β-casein aggregation. About digestion, when we consider only Maillard Reaction, we show that proteolysis was impaired by glycosylation. When β-Lg was heated with αS2-CN or κ-CN, we observed that homo- or hetero- aggregates were formed. Finally, the digestion of the mixed aggregates did not change when different proteins were heated together; even a slight increase of susceptibility to proteolysis was noted. These fundamentals studies highlighted some possible protein/sugar and protein/protein interactions during heat treatment, and give more details on the possible chemical transformations that occur during severe or cumulative heat treatments. Further, information about digestion of the aggregates may assist future studies about allergenicity or availability of milk proteins.