The dairy industry has long known that highly concentrated alkaline solutions should not be used to clean whey protein rich fouling deposits. At >0.1 mol L−1 NaOH dissolution and cleaning rates decrease markedly to very low values, particularly at low-mid temperatures. It is shown here that it is caused by the incapacity of the hydroxide ion to destroy non-covalent interactions between protein aggregates at high alkali concentrations. HPLC is used to quantify the breakdown kinetics of soluble whey protein isolate (WPI) aggregates. Results show that the large aggregates breakdown kinetic constant is strongly reduced at >0.25 mol L−1 NaOH, but also at high protein concentrations. Moreover, large aggregates become increasingly stable for long times at ≥0.5 mol L−1 NaOH. The kinetic analysis predicts that large protein aggregates would be fully stable at 0.085–0.105 g WPI/g solution, explaining the dissolution threshold observed in macroscopic swelling studies.