Oxidized glutathione (GSSG), which has four carboxylic and two amino groups, interacts with metal ions and may affect the bioavailability and geochemistry of metals in natural waters. In the present paper, six stepwise protonation constants K H i for GSSG were measured as a function of salinity, S = 5-35% at t = 25°C (and in NaCl/ MgCl 2 mixtures at different ionic strengths), in order to provide thermodynamic data for their acid base properties, which are useful for studying the interaction with metals in these media. The protonation enthalpies (DH i /kJ mol -1 ) were also determined at t = 25°C. The results were interpreted using the SIT model and Pitzer equations. The seawater model with the interaction parameters accounts for the differences between the values in NaCl and seawater. The results suggest that it is important to consider all of the ionic interactions in natural waters in examining the proton dissociation of GSSG.