The interaction of iron oxide nanoparticles with an aqueous medium has been studied. The composition of the nanoparticles corresponds to magnetite–maghemite solid solutions with different Fe 2+ /Fe 3+ ratios. Nanoparticles that most closely correspond to the composition of maghemite (γ-Fe 2 O 3 ) have largest hydrodynamic diameters and cause a drastic decrease in the pH of the dispersion medium during the dispersion of the powders in water. Nanoparticles that have a phase composition of a solid solution corresponding to the middle of the magnetite–maghemite series are characterized by a gradual and less pronounced decrease in pH. It has been shown that dilution of aqueous suspensions obtained from preliminarily dried powders within a concentration range of 100–0.001 mg/L followed by sonication leads to a significant increase in the hydrodynamic diameter of iron oxide particles. A possible mechanism of the studied interaction of nanoparticles with the aqueous medium has been considered. This mechanism comprises the hydration of Lewis acid sites formed by iron ions and changes in the character of the dissociation of hydroxyl groups depending on the pH of a suspension. The effect of surface passivation of the studied nanopowders with oleic acid on the processes under consideration has been investigated. The results obtained make it possible to predict the aggregative stability and a number of other characteristics of the studied suspensions being diluted with water.