Distribution of 29 drug compounds was examined in octanol-buffer systems of eight different ionic compositions at pH 7.4. It was found that the ionic composition of the octanol-buffer system has a noticeable and unpredictable effect on the logD7.4 values for different compounds. It is established that the response of compounds to different ionic environments displayed as logD7.4 values are linearly interrelated similarly to different properties of compounds in the organic solvent-free aqueous solutions reported previously [Ferreira et al., Phys. Chem. Chem. Phys. 2014, 16, 23347]. Analysis of the role of different structural features of compounds examined in their ionic responsiveness showed that molecular polarizability and polar surface area are the two most important features. It is suggested that the relationships reported here and previously are based on the same physical principles that must be taken into account in any theoretical model of solute-water interactions in aqueous solutions containing salt additives.