Investigation of the acid–base behaviour of proteins can result in information on both their composition and the concentration. Volumetric titration is the standard method to obtain this kind of data. In this paper four different ways of protein titration are presented, applied on membrane-covered ISFETs. Two of these methods are based on coulometric titrant generation, produced by an integrated actuator, while the two other methods presented here are based on the external application of either a pH-step or an ion-step. It is experimentally shown, that some methods reveal information especially on the composition of the protein, whereas other methods are better suited for concentration determination.